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Review

Psidium guajava L. An Incalculable but Underexplored Food Crop: Its Phytochemistry, Ethnopharmacology, and Industrial Applications

by
Muhammad Imran Tousif
1,
Mamona Nazir
2,
Muhammad Saleem
3,
Saba Tauseef
4,
Nusrat Shafiq
5,
Laiba Hassan
6,
Hidayat Hussian
7,
Domenico Montesano
8,*,
Daniele Naviglio
9,*,
Gokhan Zengin
10 and
Ishtiaq Ahmad
11
1
Department of Chemistry, Division of Science and Technology, University of Education, Lahore 54000, Pakistan
2
Department of Chemistry, Govt. Sadiq College Women University Bahawalpur, Bahawalpur 63100, Pakistan
3
Division of Organic Chemistry, Institute of Chemistry, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
4
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
5
Department of Chemistry, Government College Women University Faisalabad, Faisalabad 38000, Pakistan
6
Department of Pharmacy, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
7
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle, Germany
8
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy
9
Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 4, 80126 Naples, Italy
10
Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey
11
Department of Chemical Engineering and Biotechnology, University of Cambridge, Philipa Fawcett Drive, Cambridge CB3 0AS, UK
 
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Authors to whom correspondence should be addressed.
Molecules 2022, 27(20), 7016; https://doi.org/10.3390/molecules27207016
Submission received: 12 September 2022 / Revised: 28 September 2022 / Accepted: 8 October 2022 / Published: 18 October 2022
(This article belongs to the Special Issue Analysis of Bioactive Compounds in Food)
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Abstract

:
Psidium guajava L. (guava) is a small tree known for its fruit flavor that is cultivated almost around the globe in tropical areas. Its fruit is amazingly rich in antioxidants, vitamin C, potassium, and dietary fiber. In different parts of the world, this plant holds a special place with respect to fruit and nutritional items. Pharmacological research has shown that this plant has more potential than just a fruit source; it also has beneficial effects against a variety of chronic diseases due to its rich nutritional and phytochemical profile. The primary goal of this document is to provide an updated overview of Psidium guajava L. and its bioactive secondary metabolites, as well as their availability for further study, with a focus on the health benefits and potential industrial applications. There have been several studies conducted on Psidium guajava L. in relation to its use in the pharmaceutical industry. However, its clinical efficacy and applications are still debatable. Therefore, in this review a detailed study with respect to phytochemistry of the plant through modern instruments such as GC and LC-MS has been discussed. The biological activities of secondary metabolites isolated from this plant have been extensively discussed. In order to perform long-term clinical trials to learn more about their effectiveness as drugs and applications for various health benefits, a structure activity relationship has been established. Based on the literature, it is concluded that this plant has a wide variety of biopharmaceutical applications. As a whole, this article calls for long-term clinical trials to obtain a greater understanding of how it can be used to treat different diseases.

1. Introduction

The scientific community’s interest in plant growing is particularly with regard to the chemical components of bioactive compounds, their effect on pathogens and their application as functional foods and/or nutraceuticals to human health [1]. In addition, as various food sources, plant products provide several health benefits. Psidium guajava L., commonly known as guava is a small tree, and is grown in tropical areas of world due to its fruits. Guava leaf tea and some complementary items are available in many stores in Japan [2], as it is considered that phenolic compounds of guava leaves can resolve particular health issues such as the modulation of blood sugar levels [3]. In addition to being a healthy and tasty food, the fruit is an excellent source of dietary fiber. Eating guavas may aid healthy bowel movements and prevent constipation [4]. One guava per day can provide 12% of the recommended daily intake of fiber [5]. Additionally, P.guajava L. has many applications which make this plant very important from scientific point of view. Thus, a review covering the literature of recent 7 years has been accomplished. For this purpose, a comprehensive literature survey from 2015 to 2021 was performed with respect to its health benefits, GCMS and LC-MS based phytochemical profiling and bioactive secondary metabolites isolated from the different parts of the plant. The pharmacological activities of various plant parts are also discussed in this article. Further prior reviews of this amazing plant do not describe the plant’s full potential, and hence the gaps left by these reviews are filled by the present article where all-important aspects of P. guajava are describe comprehensively.

1.1. Review Methodology

The scientific literature has been extensively investigated by the use of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases have been searched from 2015 to 2020, including Ovid (Books, Journals, Cochrane, AMED, Embase, and MEDLINE), Scopus, Google Scholar, PubMed and Science Direct. To ensure the inclusion of corresponding works, search terminologies were “Psidium guajava L.”, “chemical profiling through GCMS and LC-MS”, “essential oils and GCMS analysis”, “phytochemicals”, “meroterpenoids”. Prime research was carried out for Psidium guajava L. It was later joined by pharmaceutical or biological activity; medicinal use or traditional or toxicity or cytotoxicity. To combine the search terms, Boolean operators were used. The literature was also searched manually using a backward and forward approach to the investigation of the gray field.

1.2. Morphology of P. guajava L.

P. guajava L. of the plant family Myrtaceae belongs to the genus Psidium, which consists of about 150 species. The P. guajava L. (guava) is the most important member of this genus [6]. History revealed that this plant is originated from southern Mexico or Central America [7]. It was believed that Spanish and Portuguese took this fruit to other parts of the world. Its adaptability to different environments in the world is important factor which makes it worldwide fruit in tropical and sub-tropical regions of the globe. The subcontinent, especially, is a great home for this fruit. Guava plant is an evergreen shrub or tree with 3–10 m height. Its leaves are 4–10 mm long and oval in shape. The flowers are pure white, having five petals and long, multiple central stamens. Its fruit is a berry and medium to large in size with a weight around 100–250 g. Fruit shape may be spherical, ovoid or pyriform depending on the type of plant. Skin of the fresh fruit is dark green which changes to light green-yellow, pale yellow and pure yellow based on the cultivar. The aroma of the fruit is pleasant, and a seed cavity is present in the center of the fruit. The fruit pulp is soft and white to red in color depending upon the type of cultivar.

1.3. Nutritional Assessment and Traditional Uses of P. guajava L.

P. guajava is cultivated as fruit crop and as medicinal plant. Its fruit has economic significance due to pleasant aroma and taste and is used in production of juice, nectar, paste, jam, jelly and candy bars. The nutritional composition of different parts of guava is given in Table 1, which indicates the high value of the fruit and seeds. Further, the fruit and leaves have great medicinal importance and are used to treat various aliments associated with the stomach. Its leaf extracts have strong antibacterial effect [8]. Guava plant is considered to be an excellent source of ascorbic acids, phenolic compounds and carotenoids with major role in the prevention of most the chronic diseases. Crude fiber in guava is 30.9%, which makes it a good source of antioxidant dietary fiber.
The major uses of the main producing countries for guava leaves are for treatment of diabetes mellitus, cardiovascular diseases, cancer and parasitic infections [4]. The application of the treatment is either oral or topical, depending on the disease. In India, China, Pakistan, and Bangladesh, ingestion through decoction, infusion and boiled preparations is the most common way to resolve many illnesses, such as rheumatism, diarrhea, gastrointestinal problems, diabetes mellitus, infections, inflammatory disorders and cough [8,9,10,11]. The decoction of leaves is used for mouth ulcers in Southeast Asia [8,10,11]. Poultice is externally used in Mexico, Brazil, Philippines, and Nigeria for skin and wound applications. In addition, in Nigeria, it is anti-bactericidal agent and chewing sticks are used for oral treatment [8,9,10,11].
Table
Table 1. Nutritional composition of different parts of P. guajava L.
Table 1. Nutritional composition of different parts of P. guajava L.
The Major Nutritional Composition of P. guajava L. Whole Fruit
Nutritional Components% of Component/100 gReferences
Sugars (g/100 g)8.92[12]
vitamin C (mg/100 g)228.3
vitamin A (IU/100 g)624
Vitamin E (mg/100 g)0.73
vitamin K (μg/100 g)2.6
Lycopene (in red-fleshed cultivars only); (mg/100 g)5.2
Potassium (mg/100 g)417
Phosphorus (mg/100 g)40
Magnesium (mg/100 g)22
Calcium (g/100 g)18
The major nutritional composition of P. guajava L. fruit Pulp
Protein (g/100 g)0.3
5.13 ± 0.26
0.88		[13,14,15]
Carbohydrates (g/100 g)15
13.2
Vitamin A (IU/100 g)109
200–400
Thiamine (B1) (mg/100 g)0.06
0.046
Riboflavin (B2) (mg/100 g)0.06
0.03–0.04
Niacin (B3) (mg/100 g)1.3
0.6–1.068
Ascorbic acid (C) (mg/100 g)190
100
Calcium (mg/100 g)15
9.1–17
Phosphorus(mg/100 g)16
17.8–30
Iron (mg/100 g)0.3
0.30–0.70
Potassium (mg/100 g)292
Sodium (mg/100 g)6
Calories kcal/100 g54.97
36–50
The major nutritional composition of P. guajava L. seeds
Protein (g/100 g)11.19
4.8 ± 0.10
7.71		[16,17,18,19,20]
Carbohydrates (g/100 g)22.2 ± 0.14
11.51
Vitamin A (IU/100 g)50.13
Niacin (B3) (mg/100 g)0.16
Ascorbic acid (C) (mg/100 g)87.44
0.20
Zinc (mg/100 g)3.31
Calcium (mg/100 g)0.05 ± 0.14
60.07
Phosphorus(mg/100 g)160.55
Iron (mg/100 g)13.8
3.32
Potassium (mg/100 g)300
Calories kcal/100 g182

2. Phytochemistry of P. guajava L.

2.1. LCMS Analysis of the Leaves Extract of P. guajava L.

The literature revealed that UPLC-ESI-QTOF-MS analysis of the leaves extract of P. guajava disclosed fourteen compounds (Table 2) of phenolic class of secondary metabolites [21], while in another report, the chemical profiling by HPLC-PDA and LC-TOF-MS (negative and positive modes) showed the presence of altogether 21 compounds (Table 2) from seven P. guajava cultivars [22]. Study on pink guava (P. guajava L.), the phytochemical investigation through ultra-high performance liquid chromatography with diode array result in identification of 60 phenolics with different structural features, such as flavonoids, ellagitannins, flavones, flavonols, flavanols, proanthocyanidins, dihydrochalcones and anthocyanidins, stilbenes, acetophenones, and benzophenones. Out of all these identified compounds 42 polyphenols were reported for the first time in both peel and flesh, and 24 compounds were detected for the first time in P. guajava [23]. However, various chemical profiling of different cultivars of guava have shown the presence of phenolic compounds in major amounts. The dominant phenolic metabolites were assumed to be responsible for its strong antioxidant and antidiabetic activity.

2.2. GCMS Analysis of the Leaf Extracts of P. guajava L.

GCMS analysis of the ethanolic extract of guava leaves results in identification of 33 phytochemicals (Table 3). Further studies of ethanolic and aqueous extracts showed the presence of tannin, saponin, polyphenol, flavonoids, steroids, carbohydrate, terpenoids, triterpenoids and glycoside in both the extracts. The quantitative analysis showed phenolics as major constituents (9.33 mg/gm powder), followed by flavonoids (6.42 mg/gm powder), tannin (4.30 mg/gm powder) and saponin (3.67 mg/gm powder) and [24]. Other investigators reported nine compounds through GCMS analysis, which are presented in Table 3. The estimation of total phenolic showed that polyphenolic is present in high amount as in methanol fraction (261.4 ± 8.5) followed by the ethanol (146.7 ± 2.2), ethyl acetate (99.6 ± 2.4), acetone (84.2 ± 2.4), benzene (43.8 ± 2.3) and petrol ether (41.2 ± 1.9) fractions [25]. Ashraf et. al., in 2016 has published the chemical composition of the different extracts of leaves by GCMS and identified the 33 compounds. Further total phenolic contents (mg GAE/mg of plant extract) of methanol (83.34 ± 0.49), chloroform (71.49 ± 0.48) and hexane (53.24 ± 2.05) were determined. The total flavonoids contents (mg QE/mg of plant extract) of methanol, chloroform and hexane were 53.39 ± 0.89, 32.76 ± 1.15, 21.26 ± 1.49 respectively [26]. Another study conducted in 2018 for chemical profiling of the leaves of the guava showed the presence of total nine compounds as presented in Table 3 [27,28]. The analysis of GCMS studies showed interesting data as except some major components such as α-Copaene, Caryophyllene, Epiglobulol, Ledol, Copaene and γ-Muurolene, the extracts of different region possess the different compounds. The above contradictions in results from various groups may be attributed to agro-climatic conditions of the regions, type of cultivar, maturity stage at which the plant was collected, type of extraction technique and polarity of different solvents used.

2.3. Chemical Composition of Essential Oil of P. guajava L.

During literature search, several reports were encountered highlighting essential oil compositions of guava fruit and leaves (Table 4). For example, the essential oil obtained through hydrodistillation from the leaves of P. guajava, collected from Kathmandu, Nepal, was analyzed by GC-MS. Out of 100 identified compounds 53 were major constituents and accounts for 100% of oil composition. The major phytochemicals identified from essential oil were (E)-nerolidol (35.6%) and (E)-caryophyllene (15.8%), (2Z,6E)-farnesol (6.7%), ledol (5.5%) and cubenol (3.99%) [32]. Another report describes leaf essential oil composition of P. guajava through GC-MS where 27 substances were identified with α-terpinyl acetate (23.57%), trans caryophyllene (17.65%), nerolidol (12.16%), αcadinol (6.71%), α-copaene (6.5%), α humulene (3.92%), (-)-caryphyllene oxide (3.66%), iso aroma-dendren epoxid (2.55%) and trans α-bisabolene (2.01%) as the major components. In this report, the overall % age yields of oils were obtained as 0.51% (v/w) [33]. GC-FID and GC-MS analyses of leaf essential oil identified even higher number of components i.e., 46 with major components have been reported as limonene (29.1%), (E)-caryophyllene (15.7%), caryophyllene oxide (8.8%), caryophylla-4(12),8(13)-dien-5-ol (6.5%), (E)-nerolidol (4.0%), α-cadinol (3.4%), muurola-4,10(14)-dien-1-β-ol (2.5%), 1,8-cineole (2.6%), α-copaene (2.3%) and α-humulene (2.0%) [34]., whereas, in other report it is observed that the examined essential oil from leaves of P. guajava, dominated by limonene, (E)-caryophyllene and (E)-nerolidol and their derivatives (Table 4). Since these studies were performed under different conditions and plants used were growing in different climatic conditions, it is reasonable to find varying compositions of essential oil. These variations (Table 4) correspond to climate, type of plant culture and stage at which this fruit was collected.

3. Bioactive Compounds Isolated from P. guajava L. and Their Structure Activity Relationship

3.1. Phenolics/Phenolic Acids from P. guajava L.

The published literature revealed that different research groups have studied secondary metabolic profiles of guava through LCMS/UPLCMS and other related techniques, and have reported phenolics as the major components of guava. Further reports on isolation and structure elucidation of these secondary metabolites have substantiated the above analytical results, since variety of phenolics have been isolated from various parts of this plant. For example, six guavinosides A–F (1–6) were separated from the leaf extract of the P. guajava (Figure 1), which were identified due to spectroscopic means. Compounds 3 and 6 showed good cytotoxicity against HeLa, SGC-7901 and A549 cell lines, with IC50 values of 4.277, 7.288 and 3.246 µg/mL respectively (Table 5). Comparison with potential of reference drug (Adriamycin, IC50 = 1.359, 3.118 and 2.684 µg/mL) indicated significant anticancer property of these compounds. In variety of antioxidant assays, compound 3 inhibited the FRAP, DPPH and ABTS activity On the other hand, compound 1 showed a dose dependent FRAP, DPPH and ABTS activity with IC50 values of 11.54 (12.5 µg/mL), 14.00 (25 µg/mL), 23.73 (50 µg/mL) and 46.37 (100 µg/mL), followed by significant inhibition by compound 4, while other compounds also displayed varying potential (Table 5) [36].
Acylated Phenolic Glycosides (7–17) were isolated from the leaves of the P. guajava (Figure 2), which showed DPPH Scavenged Free Radicals activity with IC50 values in the range of 84.28 to 180.00 μM. Since the standard drug ascorbic acid exhibited IC50 value of 108.60 μM, it offers a strong candidature of compounds 7–17 to be further studied for their value as antioxidant drug [37]. Compounds 2, 5 and a benzophenone galloyl glycoside (18), were isolated from the leaves of the P. guajava L. (Figure 3) by High-Speed Counter-Current Chromatography and their structure was identified through details spectroscopic data. Compound 2, 5 and 18 were tested against HCT116 and HT29 cells. Compound 2 and 18 showed good inhibitory activity against HCT116 and HT29 cells in a dose dependent and time-dependent manner up to 81.4% at dose of 100 μM after 72 h of treatment, while under same conditions, compound 2 showed less inhibition by 66.2% (Table 5). Furthermore, compound 18 was tested for cellular apoptosis of HCT116 cells and showed good increased in the size of the apoptotic cell population by 1.50-fold (3.65%), 2.33-fold (5.67%), and 10.08-fold (24.53%) at concentration of 40, 60 and 80 μM respectively. It is very important that to mention here that chemical structure of the compound 2 and 18 was nearly similar to that of 5, and thus their inhibitory potential was compared, which indicated that a trihydroxybenzoate moiety (as in 2 and 18) is required for anticancer activity of these compounds [38]. Four flavonoids (19–22) were also isolated from leaves of the P. guajava, and were evaluated for their anticancer and antioxidant activity. Compound 19 showed the FRAP activity on dose dependent manner by a value of 333.26 ± 1.76 (12.5 µg/mL), 359.18 ± 15.14 (25 µg/mL), 379.40 ± 10.31 (50 µg/mL), 401.27 ± 12.23 (100 µg/mL), Compound 20 showed the inhibition with a value of 123.88 ± 14.95 (12.5 µg/mL), 269.00 ± 7.28 (25 µg/mL), 291.63 ± 32.79 (50 µg/mL), 324.58 ± 10.64 (100 µg/mL), Compound 21 displayed the inhibition with a value of 57.21 ± 4.94 (12.5 µg/mL), 175.59 ± 7.11(25 µg/mL), 220.51 ± 22.18 (50 µg/mL), 346.45 ± 25.61 (100 µg/mL) and Compound 22 showed the inhibition with a value of 68.06 ± 5.74 (12.5 µg/mL), 155.89 ± 17.90(25 µg/mL), 287.94 ± 2.26 (50 µg/mL) and 329.68 ± 17.72(100 µg/mL), while these compounds also showed good antioxidant activities on DPPH and ABTS free radicals. The compounds 19–22 displayed the DPPH free radical activity with IC50 values of 11.00 ± 0.26, 5 16.13 ± 0.32, 6 13.43 ± 0.12 and 27.03 ± 1.70, respectively and ABTS free radical activity with IC50 values of 4.40 ± 0.26, 6.90 ± 0.36, 6.70 ± 0.26, and 10.57 ± 0.51, respectively [36].

3.2. Meroterpenoid

In addition to above phenolics mostly isolated from leaves of P. guajava L., hybrid compounds are noticed as a striking feature of this plant. Among these hybrid compounds, meroterpenoids (Table 4, Table 5, Table 6, Table 7 and Table 8) are the most attractive group of secondary metabolites, in which the terpenoidal part is bonded with other classes of secondary metabolites, especially phenolics, for example, guajavadimer A (23), a dimeric sesquiterpene-based meroterpenoid isolated from the leaves of P. guajava L. the chemical structure of the compound was established through detail spectroscopic studies and X-ray crystallography. It possessed two caryophyllenes, a flavonone-fused and a benzylphlorogulcinol complicated skeleton and showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)- induced toxicity in HepG2 cells with value of OD (mean ± SD) 1.654 ± 0.094 [39]. Diformylphloroglucinol-derived meroterpenoids psiguajavadials A (24) and B (25), guadial A–C (26–28), psiguadial B–D (29–31), guajadial (32), psidial A (33), 4,5-diepipsidial A (34), guajadial B (35) and guajadials C–F (36–39) were isolated from P. guajava L. and their structure was identified through spectroscopic analysis and ECD calculations [40]. All compounds (24–39) showed antitumor activity (Table 5) against HCT116, CCRF-CEM, DU145, Huh7, and A549 with the cell viability rates less than 50% at 60 μM concentration. Compounds 34 and 35 were the most active against A549 cells with IC50 values of 160 and 150 μM, respectively. While compounds 24, 36, 37 and 39 have same potential at 50 μM, compounds 24, 25, 35 and 39 showed dose-dependent inhibition of Top1 activity. Mechanistic study for compounds 24 and 25 displayed potent antiproliferative effects against HCT-116 cells by inducing apoptosis in a dose-dependent manner and induced antagonized Top1-mediated DNA break [41]. Guajadial (32), inhibited endothelial cell proliferation and migration, and furthermore it suppresses tumor growth in human NSCLC (A549 and H1650 cells) xenograft mouse models. This potential has been reported as significant antineoplasmic activity of 32. Western blotting method to study the underlying mechanisms of VEGF receptor (VEGFR)2-mediated revealed that compound 32 inhibited A549 (IC50 = 3.58 μM) proliferation via blocking the Ras/MAPK pathway [42]. Moreover, guadial A–C (26–28) [43,44], psiguadial B–D (22–24) [41,43], guajadial (32) [45], psidial A (33) [46], 4,5-diepipsidial A (34) [47], guajadial B (35) [48] and guajadials C–F (36–39) [49] were also previously reported from P. guajava L. Among other anticancer meroterpenoids the Diformylphloroglucinol-based guajavadials A–C (40–42) were isolated from P. guajava L. and the structures of all compounds were determined through spectroscopic studies. All compounds displayed good cytotoxicity against HL-60, A-549, SMMC-7721, MCF-7, and SW480 cancer cell lines with IC50 values between 2.28–3.38 µM (Table 5). Compound 40 exhibited the highest potential with a value of IC50 = 3.54 µM against SMMC-7721 cell lines, and this activity level is higher than the control drug cisplatin (IC50 = 19.82 µM) [50]. The structures activity relationship showed that the arrangement of the isoprene units is responsible for the activity, and thus the terpenoidal skeleton plays key role in activity potential, as can be seen in compounds 41 and 42. Guajavadial A (40) is a 3,5-diformylbenzyl phloroglucinol-coupled monoterpenoid skeleton and guajavadials B (41) and C (42) are the adducts of the 3,5-diformylbenzyl phloroglucinol and a sesquiterpene with different coupling models [50]. More meroterpenoids namely psiguajadials A–K (43–53) along with psiguadial A (54), guapsidial A (55), and psiguajadial L (56) were also isolated from P. guajava. All these natural products (43–56) has shown significant inhibition of PDE4D-4 with IC50 values ranging from 1.34–7.26 μM (Table 6) [51]. This activity potential is comparable with the rolipram, a standard PDE4 inhibitor (IC50 0.62 μM). Since a little difference has been reported in activity level of all these compounds, which may lead to the conclusion that diformylphloroglucinol moiety is required for PDE4D2 inhibitory activities (Table 6). Compounds psiguadial A (54) [41], guapsidial A (55) [44], and psiguajadial L (56) [47] were previously also reported from P. guajava produced complex and diverse meroterpenoids bearing phloroglucinol-coupled to sesquiterpenoids or monoterpenes. Similarly, here the Phloroglucinol-coupled to cubebane sesquiterpenoid core in compounds 43 and 44, and compound 45 has globulane as terpene unit, 48 has caryolane, 49 has caryophyllane, and compounds 50–52 have cadinane unit as terpene unit [51]. One more meroterpenoid Guavadial (57) was isolated of P. guajava which has caryophyllene combined to diformyl phloroglucinol core [49]. Furthermore, meroterpenoids were obtained from P. guajava L. namely Psiguajdianone (58), Psiguajanone A (59), Psiguajanone B (60), Psiguajanone C (61), Psiguajanone D (62), Psiguajanol A (63) along with the already reported Guapsidial A (55) and Psiguajadial D (44). All compounds were tested for anticancer and anti-inflammatory activity on NO, TNF-α and PEG2 production in RAW264.7 cells. All isolates showed the inhibition with a value ranging from 2.86–11.82, 1.66–31.59 and 1.08–13.63 for NO. TNF-α and PEG2 respectively [52] (Figure 4 and Figure 5).
Psiguadiols A–J (64–73), meroterpenoids were isolated from leaves of the P. guajava L., which has 6,8-diformyl-5,7-dihydroxy-4-phenylchromane-coupled sesquiterpenoids along with a C-8-spiro-fused 6/6/9/4 tetracyclic ring system. The chemical structure of the natural product was determined from spectroscopic data, ECD data, and single-crystal X-ray diffraction data. The protein tyrosine phosphatase 1B (PTP1B) is critically involved in insulin receptor signaling and an important target from treatment of DM type II. Interestingly guava meroterpenoids, psiguadiols A, G, H (64, 70 & 71) inhibited PTP1B with IC50 values of 4.7, 6.2 and 9.2 μM respectively [53], while all other compounds were found inactive. Three psiguamers A–C (74–76) sesquiterpene-based meroterpenoids bearing a rare methylated benzoylphloroglucinol and bicyclogermacrene units, were isolated from leaves of P. guajava L. Their structures were established through comprehensive analysis of spectroscopic data, electronic circular dichroism (ECD) and X-ray crystallographic data. All compounds were tested for anticancer activity but only compound (+)-74 showed strong cytotoxic activities against five human tumor cell lines; HCT-116, HepG2, BGC-823, A549, and U251 with values of IC50; 2.94, 9.01, 6.45, 5.42 and 5.33 μmol/L respectively [54]. Seventeen meroterpenoids were isolated from the leaves of the Psidium guajava including euglobal B1-1 (77), euglobal Ib (78), euglobal Ic (79), euglobal III (80), euglobal IIb (81), euglobal-Iva (82), euglobal Ivb (83), euglobal V (84), macrocarpal A (85), ecalrobusone E (86), guajadial C (36), guajadial D (37), guajadial E (38), guajudial (87), psiguajadial H (50), psiguajadial I (51), and psiguajadial J (52) were isolated from the leaves of guava [37]. Jejuguajavones A–J (88–97) isolated from the 95% EtOH extract of Jejuguava leaves and evaluated against the PTP1B enzyme. Compound 88–91 showed the good inhibitory activity with value ranging from 9.40–37.83 µM [55]. Eleven polycyclic phloroglucinol meroterpenoids guajamers A–I (98–106), along with guadial A (26) guadial C (28) were isolated from the leaves of P. guajava. All compounds were checked for antibacterial activity and 99–104, 26 and 28 showed moderate activity [56]. It is concluded from the bioactivity of the isolated compounds that P. guajava L. is excellent sources for the treatment of oxidative stress, diabetes and inflammation. Further compounds isolated from P. guajava L. leaves and their anti-cancer effects against human cancer cells, paving the way for these compounds and P. guajava L. leaves to be used as possible chemoprevention agents against cancer (Figure 6, Figure 7 and Figure 8).

4. Pharmacological Activities

4.1. Antidiabetic Potential of Leaf Extract

Literature search revealed that several studies have been carried out to evaluate pharmacological potential of guava leaves. The guava leaves have an ability to increase glycogen synthesis and halt the process of hepatic gluconeogenesis by regulating AMPK/ACC pathway in streptozotocin-induced diabetic rats, when orally administered as 200 mg/kg by weight [57]. It is further reported that guava leaves reduced triglycerides, phospholipids, free fatty acids, total cholesterol and LDL levels while HDL level was raised in STZ induced rats [57]. To validate the role of guava leaves in treatment of Diabetes Mellitus (DM), a novel purified heteropolysaccharide GP70-3M from the leaves was tested in vitro against α-glucosidase, which showed outstanding inhibitory activity with an IC50 value of 2.539 µM. This potential has been reported to be 1867 times greater than control acarbose (IC50 value of 4.744 mM). Different parts of the plant were screened for their diabetic inhibition (Table 7) [58].
Table
Table 7. Anti-diabetic potential of different parts of P. guajava.
Table 7. Anti-diabetic potential of different parts of P. guajava.
ActivityEnzymeIC50 μMPlant Part UsedReferences
Anti-diabeticα-glucosidase2.539Leaves[58]
α-glucosidase1.0Leaves[59]
α-glucosidase0.5Bark[59]
α-amylase10.6Bark[59]
Glucose-6-PhosphataseSignificantLeaves[58]
ControlAcarbose4.744 [58]
Table
Table 8. IC50 and selectivity index (SI) of essential oil of P. guajava leaves (PG-EO) against diferent cell lines.
Table 8. IC50 and selectivity index (SI) of essential oil of P. guajava leaves (PG-EO) against diferent cell lines.
Cell LineTreatment (µg/mL)
PG-EO DXR
IC50SIIC50SI
GM07492A126.4 ± 11.8-0.5 ± 0.2-
MCF-796.9 ± 8.4 a1.362.1 ± 2.0-
HeLa128.7 ± 1.5-5.3 ± 1.3-
M059J103.6 ± 5.1 a1.216.2 ± 2.5-
The leaf extract of P. guajava increased the uptake of 2-deoxy-d-[1–3H]-glucose in C2C12 muscle cells with a value of 161.4 ± 10.1%, p = 0.0015 as compared to vehicle control (dimethyl sulfoxide), and standard drugs metformin (144.0 ± 7.7%, p = 0.0345) and insulin (141.5 ± 13.8%, p = 0.0495). Furthermore, it also noted that leaf extract of P. guajava considerably enhanced the triglyceride accumulation in 3T3-L1 cells compared to standard drug (rosiglitazone) [59].

4.2. Anticonvulsant Effects

The P. guajava leaf ethanolic extract has been found to afford anti-convulsant activity; since it exerted dose dependent (200 mg/kg and 400 mg/kg) effect on seizures induced mice using MES as suggested by some parameters for example reduced hind-limb tonic extension (HLTE), increased percentage protection from induced MES convulsions. Anti-convulsant effect on Maximal Electrocshock (MES) mice model suggests that the extract has produced dose dependent anticonvulsant effect in albino mice. While in pentylenetetrazole (PTZ) induced mice model P. guajava extract prolonged the clonic convulsion latency, reduced convulsion duration in a dose dependent manner along with reduction in seizure score [60].

4.3. Antiproliferative Potential of Essential Oils from P. guajava Leaves Extracts

Essential oil obtained from leaves of P. guajava was evaluated for its antiproliferative activity against human gliobastoma (M059J), human cervical adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7) and normal human GM07492A cell lines, whereas lung fibroblasts cell line was used as control. The reported results showed that the oil exhibited significant IC50 values for M059J and MCF-7 compared to normal line as presented in Table 8 [61].

4.4. Antimutagenic Effect

The methanolic extract of P. guajava leaves tested against methyl sulfonate (MMS), sodium azide (NaN3), benzo(a)pyrene (BP) and 2-aminofluorene for its antimutagenic effect. The methanol extract of P. guajava leaf extract was found to inhibit 70% of mutagenesis at concentration of 80 mg/mL. This setup is on the basis that the phenolic contents present in P. guajava have broad-spectrum antimutagenic activity and could serve as potentially good Candidates for phytomedicine [25].

4.5. Antifungal Properties

Various published work revealed that P. guajava L. has also shown to possess some antifungal activities. Its tannins and flavonoid fraction were analyzed for antifungal activity using 21 different compounds in fraction of two, having phenolic compound in higher concentration. In an in vitro assay performed against three fungal strains of Candida i.e albicans, krusei and tropicalis through microdilution showed that IC50 values for these strains ranged from 69.29 to 3444.62 μg/mL for the isolated and combined fractions of flavonoids and tannins. While the reference compound fluconazole and combined fraction ranged from 1.57 to 925.56 μg/mL, which shows that natural products have some synergism with antifungal potential. The fractions were found to affect pleomorphism capacity as well along with inhibition of fungal strain in isolated form, enhancing the action potential of Fluconazole, reducing the concentration and hindering the morphological transition, one of the main virulence factor of Candida genus [62]. The P. guajava leaves extract was used for microbiological assays to determine IC50, inhibitory effect of associated fraction with Fluconazole against Candida species and cell viability curve through microdilution method. Antifungal bioassay performed on solid media by modifying morphological and fungicidal concentration and results ranged between 5.10 and 926.56 mg/mL revealed the effect of change in concentration effects the inhibition [21]. This suggests that P. brownianum and P. guajava can potentially be used to develop drugs to treat fungal infections [63,64].

4.6. Antiparasitic Potential

P. guajava L. and Psidium browninaum Mart ex DC leaf aqueous and hydroethanolic extracts were tested for their antiparasitic and cytotoxic potential against Leishmania braziliensis, Trypanosoma cruzi epimastigote forms, L. infantum promastigotes and fibroblasts at three different concentrations (250, 500 and 1000 μg/mL). The T. cruzi forms were not inhibited by the extracts from P. guajava L. P. guajava showed small amount of activity against both L. braziliensis and L. infantum. As for cytotoxicity aqueous decoction extract of P. browninaum showed highest percentage among all other extracts and showed mortality rate of 90.85% for fibroblast at 1000 μg/mL [65].

4.7. Anthelmintic Activity

The aqueous extract of P. guajava paralyzes the nematodes both Levamisole-sensitive and Levamisole-resistant strains of Caenorhabditis elegans, in a dose dependent manner. Different studies were carried out by applying concentration-dependent doses. At a concentration of 25 mg/mL of the P. guajava extract, 100% paralysis of the wild type worms was achieved with in 4 h. A similar effect was observed for N2 wild type and CB193 resistant worms and egg-laying ability was decreased by 40% at the same concentration. These reports disclose that P. guajava extracts have also potential anthelminic effect against nematodes [66]. Further these studies revealed the presence of triterpene responsible for anthelmintic activity. Therefore, it is also concluded that secondary metabolites from P. guajava leaves extract could serve as basis for antileishmanial drugs [67].

4.8. Antioxidant Potential

Phytochemistry of Guava showed the presence of flavonoids and phenolics, which is in agreement with antioxidant activity. The antioxidant activity for crude extract of peels, flesh and seed was 264.30 ± 5.39 μmol TE/g dw, 98.78 ± 3,40 μmol TE/g dw and 62.84 ± 2.81 μmol TE/g dw, respectively, which is nearly equal to the genotype known as Fan Retief and Advanced Selection. The crude extract of the peel part having highest antioxidant activity has a greater proportion of antioxidant compounds [68]. The products in P. guajava leaf tea (GLT) contain both phenolic forms i.e., soluble and insoluble-bound. The fermentation process via Saccharomyces cerevisiae and Monascus anka followed by hydrolysis through complex enzymes increases the soluble phenolic form. Free radical scavenging (DPPH) results of guava were found in close agreement with standard Trlox and ascorbic acid. The excellent IC50 in μM revealed the guava extract as potential anti-oxidant. Comparative studies on extracts and Trolox revealed the direct relationship with concentration. As the concentration was increased, the reducing ability was also enhanced and, like radical scavenging activity, SPFE reducing power was greater than rest of the extracts. The reducing power for SPFE = 97.86 mmol TE/g DM, SPF = 50.3 mmol TE/g DM, SPUF = 7.4 mmol TE/g DM. The reducing ability of soluble phenolics (SPF/SPFE) was higher than insoluble bound phenolics (IBF/IBFE) at same concentration. However, the reducing power for insoluble-bound phenolics of unfermented GLT (IBUF) was found to be 11.4 mmol TE/g DM which greater than IBF (2.9 mmol TE/g DM) and IBFE (3.5 mmol TE/g DM). When the extracts were tested for their inhibitory activity against α-glucosidase, the inhibitory effect was promisingly high for SPUF, but it was observed that it was much higher for fermented extract. The IC50 values for inhibition of α-glucosidase were in order SPFE (IC 50 = 11.8 µg/mL) > SPF (IC 50 = 19.2 µg/mL) > SPUF (IC 50 = 29.1 µg/mL). Moreover, insoluble-bound phenolics of fermented GLT (IBPF) and IBPFE have low inhibitory effect on α-glucosidase (i.e., IC50 = 104.4 µg/mL and IC 50 = 112.2 µg/mL respectively) as compared to insoluble-bound phenolics of unfermented GLT (IBPUF) having IC50 = 71.6 µg/mL. The IC50 value for positive control (acarbose) was significantly greater than all the extracts i.e., IC50 = 178.52 µg/mL [69].

4.9. Suppression of Osteoarthritis

The leaves extract from P. guajava and ellagic acid, a polyphenolic compound from the extract, have role in degeneration of aggrecan at the onset of osteoarthritis (OA) by halting activity of metalloproteinase and disintegrin with throbospondin-type-5. The efficacy of extract along with ellagic acid was determined on destruction of cartilage by giving extract as a constituent of diet of anterior cruciate ligament-transected rats (ACLT). The results suggested that P. guajava leaves extract have role in suppressing progression of OA in ACLT rats and inhibition of joint destruction at early stages through ellagic acid-mediation [70].

4.10. Antidiarrheal Activity

The antidiarrheal effect of P. guajava leaf extract carried out at normal rats and diarrheal rats suggested promising effect. Four groups were formed using normal rats: low-dose P. guajava leaves extract, high dose P. guajava leaves extract, control and gallic acid while 5 groups were formed using diarrheal rats: low-dose P. guajava leaves extract, high-dose P. guajava leaves extract, desmopressin, untreated control group and gallic acid. The low-dose P. guajava extract was equal to 50 mg/kg, high-dose P. guajava extract was equal to 100 mg/kg for both normal and diarrheal rats while desmopressin was used 0.2 mg/kg for a period of one month. The administration of P. guajava leaves extract to diarrheal rats stabilized all the parameters such as kidney weight decline, levels of potassium, sodium and chloride in serum, urine volume, serum urea etc. along with antidiarrheal effect P. guajava leaves extracts also aids in protein conservation [71]. According to survey, there is no single clinical trial found on intake of guava as active anti-diarrheal ingredient.

4.11. Antiestrogenic Activity

The Guajadial, meroterpenoids, from P. guajava leaves extract reported to have antiproliferative and antiestrogenic activity, the action mechanism is similar to tamoxifen which indicates it as promising therapeutic agent based on phytoestrogen. The enriched fraction of guajadial form crude P. guajava leaves extract has selectivity and antiproliferative activity in vitro against human breast cancer cell lines MCF-7 and MCF-7 BUS. The total growth inhibition for MCF-7 was 5.59 µg/mL and for MCF-7 BUS was 2.27 µg/mL. The in vivo analysis on uterus of pre-pubescent rats also confirmed the antiestrogenic activity as guajadial fraction halted the proliferative activity of estradiol [72].

4.12. Anticancer Potential

4.12.1. Anticancer Activity of Leaves Extract

The ethanolic extract of P. guajava leaves and quercetin isolated fractions reduce CCl4-induced cytotoxic effect on HepG2 cell lines. The levels of GSH, viability and cytotoxicity were reduced in CCl4 treated cell lines while lipid peroxidation, Lactate dehydrogenase (LDH), Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were increased. The levels of all these parameters were regulated in a positive manner through the application of P. guajava leaves extract [73].

4.12.2. Cytotoxic Effect of P. guajava Fruit Extract

With the useful biological effects, it is necessary to determine the cytotoxicity of any drug, formulation and nutraceutical. The P. guajava extract administered orally at 2000 mg/kg and 5000 mg/kg b.w of mice did not make any noticeable change in number of kidney podocyte, liver hepatocyte and body weight. The extract from P. guajava leaves extract is safe to use as it non-toxic to both kidney and liver [74]. The aqueous extract of P. guajava leaves in the diet of Oreochromis niloticus not only increased body weight but also increased the villi surface area by increasing its length and width. The immune response and antioxidant activity were improved as total protein content (glutathione S-transferase, superoxide dismutase, and glutathione peroxidase) increased. The Aeromonas hydrophila, a pathogen towards O. niloticus, inhibited by the presence of P. guajava leaves extract, while the absence of extract in the diet of fish increased the mortality rate [75]. In 2019 Babatola et al. also evaluated the toxicity of aqueous leaves extract of three different species of guava i.e., pink, red and white. The rats were used as test animals for this study and extract was administered at a dose of 50, 500 and 5000 mg/kg bodyweight for a period of 14 days. Observation of experimental periods showed effect on parameters accounted and found no toxic effects with a slight increase in body weight but no deaths. The estimated LD50 was found to be 50–5000 mg/kg for these pink, red and white leaves extract of guava [76].

4.13. Antiviral Activity

The antiviral selectivity of P. guajava leaves extract was determined against herpes simplex virus 1 and human immunodeficiency virus, and median cytotoxicity and half-maximal effective concentration were obtained. The EC50 values for HIV-1 strains and HSV-1 were ranged between 0.05 and 3 mg/mL and below 0.2 mg/mL respectively. Antiviral activity of guava extract was found to be based on flavonoid and phenolic contents as HPLC analysis results revealed the presence of phenols (0.8 to 2.1 GAE mg/mL) and flavonoids (62.7 to 182.1 Rutin Eq mg/g DW) [77]. Some direct studies on P. guajava isolated compounds quercetin, catechin, and gallic acid have antiviral activity against Dengue virus. The catechin is best among the three of them as it showed 100% inhibition (pre-treatment) and 91.8% inhibition (post-treatment) depending upon the experimental strategies [78].

4.14. Antibacterial Activity

In 2019, a study conducted by E. A. J. Silva and his colleagues evaluated antibacterial activity for essential oil present in P. guajava leaves. The essential oil has shown moderate activity for various genus of Streptococcus. The activity was described in terms of MIC values S. sobrinus has MIC value of 100 µg/mL, S. mitis has MIC value of 200 µg/mL, S. mutans has MIC value of 200 µg/mL), S. salivarius has MIC value of 200 µg/mL and sanguinis has MIC value of 400 µg/mL [61]. The crude extracts obtained from P. guajava leaves were evaluated for antimicrobial activities by Priscilla Alexander et al. 2019 have evaluated the antimicrobial activities. Crude extractions have mixed fraction of saponins, flavonoids, tannins, glycosides, terpenoids and steroids. The antimicrobial screening showed that crude extracts were strongly active against S. faecalis, E. coli and S. aureus having MIC value of 5.00 mg/mL. In contrast, ethanolic extracts were more actively involved in inhibition and mean zone values were found out to be 6.72 ± 0.01 for S. faecalis and 10.44 ± 0.02 for E. coli [79]. P. guajava have also been tested for its antibacterial activity as a toothpaste. Three different formulations (F) were made F1, F2 and F3 having leaves powder of P. guajava 10, 15 and 20 mg respectively. Therefore, results revealed that the antimicrobial potential against Streptococcus mutants, Streptococcus oralis, Proteus vulgaris, Bacillus subtilis and Staphylococcus aureus strains concentration dependent and F3 formulation found best one. Among all bacterial strains, the best inhibition found for Proteus vulgaris i.e., 1.1 cm while lowest zone inhibition was found against Staphylococcus aureus i.e., 0.5 cm [28]. Therefore, Patel et al. 2019 investigate an important factor regarding the medium of extraction and he evaluated the water extract of P. guajava leaves as anti-infective against Staphylococcus aureus and Pseudomonas aeruginosa present in Caenorhabditis elegans nematode host. The extracts were prepared through three different methods i.e., Decoction, Vacuum Assisted Extraction (VAE) and Microwave Assisted Extraction (MAE). The proved that extracts prepared through MAE showed better activity while its anti-infective activity was than compared to hydroalcoholic extract against five pathogenic bacteria, which were obtained using same extraction technique. Both the extracts had capability to reduce the virulence of all strains (Serratia marcescens, S. aureus, Chromobacterium violaceum, and P. aeruginosa) except S. pyrogens towards C. elegans (Table 9). This lead to reveal the method of extraction effects the activity. According to them, it seems that anti-infective property of these extracts is somehow related to property of quorum modulation that can modulate production of pigments related to quorum sensing within these susceptible bacteria [80,81].

4.15. Acute and Sub-Acute Toxicity of P. guajava Leaves Extract

The acute and subacute toxicity level of P. guajava bark extract was evaluated using Wistar rats. The extract was proved non-toxic and non-lethal and estimated LD50 was found to be >5000 mg/kg body weight for acute toxicity. The variations in relative weight of organs, body weight and other biochemical parameters that were significant were taken into account in treated animals and control group. Single dose administration at 5000 mg/kg body weight is non-toxic while repeated administration at 1000 mg/kg body weight produced sex-specific toxic effect i.e., minor liver inflammation was observed in females. Hence Psidium plant proved to have mild organ toxicity but have hepatoprotective and hematological potency [82].

4.16. Antimicrobial Activity of Essential Oils of P. guajava Leaves

The essential oils present in leaves of P. guajava have known to have cytotoxic and antimicrobial activities. Their antimicrobial activity was determined against three Gram-positive (Streptococcus aureus, Enterococcus faecalis and Staphylococcus aureus) and three Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa and Haemophilus influenzae). The antimicrobial activity of oil was significant against both Gram-positive and Gram-negative strains and ranges between 0–13 mm while no cytotoxicity was observed using brine shrimp lethality bioassay [83]. The essential oil reportedly inhibit two bacterial human pathogens with MIC values that range from 0.065–0.261 mg/mL while it also inhibits some pathogenic fungi in plants i.e., 82.80% inhibition of Fusarium chlamydosporum and 86.02% inhibition of Curvularia lunata [34].

4.17. P. guajava Leaves Activity against Diarrhea

An antidiarrheal activity of P. guajava leaves was clinically measured and three different doses (6-leaf, 10-leaf, and 14-leaf) of P. guajava leaves decoction extracts were used to their ability against diarrhea. The 14-leaf (7.4 g) decoction proved to be the most successful in the testing. Patients who received the decoction three times per day were able to return to normalcy in 72 h as opposed to 120 h for controls. Haemoglobin, liver, and kidney indicators were all within normal limits, which demonstrated the intervention’s safety [84].

5. Industrial Applications of P. guajava

Dyes and pigments are used in numerous industries worldwide, although the discharge of these materials presents significant risks to the natural environment. Nowadays, water contamination is one of the main causes of environmental pollution. Different synthetic dyes are released directly into natural water resources that are potentially pollutant the resources and make it unfit for domestic and agricultural use. On the other hand, the aromatic structures of these dyes give them greater stability and their degradation process is very slow. Further their oxidation through different oxidizing agents is not easy. Thus, these materials become main pollutants to environments. So, there is a crucial need to find environmentally friendly and cost-effective materials and methods to remove these materials from environment. P. guajava L. leaves nanocomposites materials were widely studies for decontamination of these pollutants. In a recent study a silver: iron oxide (α-Fe2O3-Ag) nanocomposite was prepared for decontamination of chromium (VI) ions from water. Further it is observed that the Cr(VI) adsorption on Fe2O3-Ag surface is endothermic and spontaneous in nature. The adsorbed Cr(VI) can easily be recovered (α-Fe2O3-Ag) nanocomposite and used up to five times [85]. In another study P. guajava leaves were used as biosorbents for the removal of Brilliant Green (BG) [86]. Magnetic nanohybrid composite γ-Fe2O3@GL was prepared by incorporated the Maghemite nanoparticles into framework of P. guajava leaves. γ-Fe2O3@GL was developed for water purification and found efficient for adsorption of methylene blue [87].
Plant-derived proteases are widely used in food and pharmaceutical industries. The upward requirement for biologic-based enzymes, in the food and pharmaceutical industries, has made them an interesting topic for physiologists and biochemists. The existence of two pH optima of P. guajava leaves protease suggests that at least two major proteases are present in it [21]. An environmentally friendly and cost-effective material CuONPs was biosynthesized by using P. guajava L. leaf. It showed potential antibacterial activity against Gram-positive and Gram-negative bacteria. It is non-toxic and exhibited good photocatalytic degradation for Congo red (CR) and methylene blue (MB). The SnO2 nanoparticles within the size of 8 to 8 nm were synthesized by using P. guajava L. leaves extract. These nanoparticles photocatalytic activity was analyzed and found effective for photo degradation of reactive yellow 186. A novel, eco-friendly cotton gauze fabric was synthesized by using P. guajava leaves powder extract. The outer membrane of Biocompatible microcapsules was synthesized from P. guajava leaves powder extract, starch core and calcium-alginate (Ca-alginate). This product was found effective for medical uses. Another novel, eco-friendly and cost-effective material, tungsten oxide nanorods (WO3 NRs), was synthesized by using P. guajava leaves extract. These nanorods were found prodigious in photocatalytic degradation of reactive green 19 (RG 19) dye.

6. Conclusions and Future Prospects

The results demonstrated that almost all parts of P. guajava are rich in diverse secondary metabolites, especially phenolics, flavonoids, squalene and vitamin E. This feature makes the plant a potential source of antioxidants to be used in nutraceuticals and functional food products. Essential oil analysis of this plant indicated the presence of caryopyllene and a variety of its derivatives, which makes P. guajava an anti-inflammatory agent. Striking feature of P. guajava is that all its parts are rich in meroterpenoids specially derived from phloroglucinol, which are mainly produced by different fungi with immunosupressive activity. Leaf and bark extracts can be used as a natural source of α-glucosidase inhibitors. In addition, the bark extract of P. guajava was an effective α-amylase inhibitor. Moreover, P. guajava leaf extract improved glucose uptake in muscle cells, while both leaf and bark extracts enhanced the triglyceride content in adipocytes in culture. P. guajava leaf and bark extracts may thus hypothetically have future applications in the treatment of type 2 diabetes. Similar to this, meroterpenoids’ isolation and activity against many cancer cell lines make it a crucial source for the development of anticancer drugs. The domestic applications of leaves also indicate its important in the field of medicine. Additionally, its applications in industry for the development of numerous beneficial products makes it a significant source that demands special consideration from the scientific community. Overall, it can be said that P. guajava is a useful plant and a rich supplier of nutrients for human growth.

Author Contributions

Conceptualization, M.I.T., M.N. and M.S.; methodology, S.T., N.S. and H.H.; software, M.I.T. and H.H.; validation, M.I.T., N.S., H.H. and G.Z.; formal analysis, M.I.T. and I.A.; investigation, M.I.T., G.Z., D.M. and D.N.; resources, M.S., H.H. and I.A.; data curation, I.A.; writing—original draft preparation, M.I.T., M.N., M.S. and L.H.; writing—review and editing, H.H., D.M., D.N. and G.Z.; visualization, H.H.; supervision, I.A.; project administration, M.I.T.; funding acquisition, D.M. and D.N. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Molecules 27 07016 g001 550
Figure 1. Isolate from the leaves extract of the P. guajava L.
Figure 1. Isolate from the leaves extract of the P. guajava L.
Molecules 27 07016 g001
Molecules 27 07016 g002 550
Figure 2. Acylated Phenolic Glycosides (7–17) were isolated from the leaves of the P. guajava L.
Figure 2. Acylated Phenolic Glycosides (7–17) were isolated from the leaves of the P. guajava L.
Molecules 27 07016 g002
Molecules 27 07016 g003 550
Figure 3. Benzophenone galloyl glycoside (18) and flavonoids (19–22) were isolated from the leaves of the P. guajava L.
Figure 3. Benzophenone galloyl glycoside (18) and flavonoids (19–22) were isolated from the leaves of the P. guajava L.
Molecules 27 07016 g003
Molecules 27 07016 g004 550
Figure 4. Meroterpenoids isolated from P. guajava L.
Figure 4. Meroterpenoids isolated from P. guajava L.
Molecules 27 07016 g004
Molecules 27 07016 g005 550
Figure 5. Meroterpenoids isolated from P. guajava L.
Figure 5. Meroterpenoids isolated from P. guajava L.
Molecules 27 07016 g005
Molecules 27 07016 g006 550
Figure 6. Meroterpenoids isolated from P. guajava L.
Figure 6. Meroterpenoids isolated from P. guajava L.
Molecules 27 07016 g006
Molecules 27 07016 g007 550
Figure 7. Meroterpenoids isolated from P. guajava L.
Figure 7. Meroterpenoids isolated from P. guajava L.
Molecules 27 07016 g007
Molecules 27 07016 g008 550
Figure 8. Meroterpenoids isolated from P. guajava L.
Figure 8. Meroterpenoids isolated from P. guajava L.
Molecules 27 07016 g008
Table
Table 2. Phytochemicals identified through LCMS studies of the Fresh Leaf of P. guajava (A).
Table 2. Phytochemicals identified through LCMS studies of the Fresh Leaf of P. guajava (A).
Sr. No.Rt (min)CompoundReferences
UPLC-ESI-QTOF-MS analysis of the leaves extract of P. guajava
10.98HHDP glucose Isomer[21]
21.865Gallic acid
32.421Galocatechin
43.197Catechin
54.08Quercetin-galloylhexoside Isomer
64.292Ellagic acid
74.665Reynoutrin
85.557Guavinoside B
96.8899(S),12(S),13(S)-Trihydroxy-10 (E),15(Z)-octadecadienoic acid
109.839Naringenin
112.430Gallocatechin
122.877Procyanidin B Isomer
134.387Quercetin
146.0052,6-dihydroxy-3-methyl-4-O-(600-O-galloyl-b-d- glucopyranosyl)benzophenone
Phytochemicals identified through HPLC-PDA and LC-TOF-MS (negative and positive modes) in the P. guajava cultivars.
1514.3Delphinidin 3-O-glucoside[22]
1615.1Cyanidin-3-O-glucoside
1716.0Myricetin-3-O-b-d-glucoside
1817.1Myricetin-3-O-arabinoside
1918.3Myricetin-3-O-xyloside
2019.0Quercetin-3-O-galactoside
2119.5Quercetin-3-O-glucoside
2220.0Quercetin-3-O-a- arabinoside
2320.6Avicularin
2421.0Isorhamnetin-3-O-glucoside
2521.9Isorhamnetin-3-O-galactoside
2624.0Abscisic acid (co-injection)
2726.1Quercetin (co-injection)
2826.4Pinfaensin
2927.8Gallocatechin-(4a-8)gallocatechol
3028.6Turpinionosides A
3129.1Pedunculoside
3230.6Gallocatechin-(4a-8)catechin
3335.6Guavenoic acid
3438.5Madecassic acid
3545.2Asiatic acid
Compounds identified in peel and flesh of ripe pink guava (P. guajava L. cv. ‘Criolla’).
Phenolic acid derivatives
361.80Galloyl-hexoside[23]
372.10Galloyl-hexoside
383.01Gallic acidd
395.70Galloyl-pentoside
407.40Hydroxybenzoyl-galloylglucoside
4111.25Dimethoxycinnamoyl-hexoside
4211.30Dimethoxycinnamoyl-hexoside
Flavones
4311.95Chrysin-C-hexoside
Ellagitannins
4413.75Valoneic acid bilactone
Flavonols
4512.16Quercetin-galloyl-hexoside
4612.30Quercetin-hexoside
4712.50Quercetin-hexoside
4812.90Quercetin-glucuronide
4913.39Quercetin-pentoside
5013.60Quercetin-pentoside
5113.92Quercetin-pentoside
5216.67Quercetin-galloyl-pentoside (guavinoside C)
5317.95Quercetin-deoxyhexoside-hexoside
5418.63Quercetin
Monomeric Flavanols
554.50Gallocatechin
566.01Epigallocatechin
5716.55Catechin
587.81Epicatechin
599.50Gallocatechin gallate
6010.53Epigallocatechin gallate
6111.63Catechin gallate
6213.47Epicatechin gallate
Proanthocyanidins
632.71PAC B-Type (E)GCg-(E)GC
643.81PAC B-Type (E)GC-(E)GC
654.64PAC B-Type (E)GC-(E)GC
664.93PAC B-Type (E)GC-(E)C
675.03PAC B-Type (E)GC-(E)C
685.48PAC B-Type (E)C-(E)GC
695.97PAC B-Type (E)GC-(E)C
706.79PAC B-Type (E)GC-(E)GC
716.80PAC B-Type (E)C-(E)C
727.07PAC B-Type (E)C-(E)GC-(E)GC
737.26PAC B-Type (E)Cg-(E)C
748.32PAC B-Type (E)C-(E)GC
758.44PAC B-Type (E)GC-(E)C
768.67PAC B-Type (E)C-(E)C-(E)C
7710.28PAC B-Type (E)C-(E)C
7813.10PAC B-Type (E)Cg-(E)GC
7914.35PAC B-Type (E)Cg-(E)GC
8020.07PAC B-Type (E)C-(E)GC
Dihydrochalcones
8112.00Phloretin-C-glucoside (nothofagin)
Table
Table 3. GCMS analysis of the leaves extracts of Psidium guajava.
Table 3. GCMS analysis of the leaves extracts of Psidium guajava.
Peak No.R. TimeArea %NameReferences
GCMS analysis of the ethanolic extract of guava leaves
13.5820.37Butanoic acid, 2-methyl-, methyl este[29]
28.4360.57dl-Limonene $$ Cyclohexene, 1-me
38.5341.371,8-Cineole $$ 2-Oxabicyclo [2.2.2]
411.7830.20(E)-2,6-Dimethyl-5,7-octadien-2-ol
514.0130.34Cyclohexasiloxane, dodecamethyl-
615.5550.22Alpha.-Copaene
716.77619.76Trans-Caryophyllene
817.7932.44Alpha.-Humulene
918.4381.12Germacrene d
1019.1157.48Trans-alpha.-bisabolene
1119.2330.44Aromadendrene 2 $$
1219.3519.75Beta.-Bisabolene
1319.9491.19Delta.-Cadinene
1420.1240.36(-)-Endo-2,6-dimethyl-6-(4-methyl-
1520.3811.09CIS-.alpha.-bisabolene $$
1620.92321.87Nerolidol B (CIS OR TRANS
1721.80310.55(-)-Caryophyllene oxide
1822.1740.35Trans-Caryophyllene
1922.4440.59Humulene oxide $$
2022.8070.69Germacrene d
2122.9170.68Tricyclo [3.3.1.13,7]decane, 2-brom
2223.0993.29(+)-Aromadendrene
2323.2024.93Torreyol $$ 1-Naphthalenol
2423.4411.91Globulol $$ (-)-Globulol
2523.6311.46Beta.-Bisabolol
2623.9631.36Alpha.-bisabolol
2725.7110.202-Methyl-6-(trimethylsilyl)benzophe
2826.5120.928-Acetyl-3,3-epoxymethano-6,6,7-t
2927.2230.351,2-Benzenedicarboxylic acid, dibut
3028.6711.891,2-Benzenedicarboxylic acid, buty
3132.6000.71Propionic acid, 2-isopropo
3238.2680.82Bis(2-ethylhexyl) phthalate
3348.5210.72Hexadeca-2,6,10,14-tetraen
Components of P. guajava methanol fraction as identified by GC-MS analysis.
343.4310.482-Nonanone[25]
353.491.301-Heptanamine
3613.843.107-Oxabicyclo [4.1.0] heptanes, 3-oxir
3715.195.132-Diethylamino-4-phenylthiooct-2-e
3815.2714.294-Methylthiazole
3918.894.422-Propenoic acid, 3-phenyl-, (E)-
4019.2311.6213-Tetradecenal
4119.447.102-Butyne, 1,4-dichloro
4221.322.601,2-Benzenedicarboxylic acid, 3-ni
Chemical components of methanol, chloroform and hexane extracts of P. guajava analyzed by gas chromatography mass spectroscopy (GC-MS).
435.19-Hydroxydimethylacetic acid[26]
4413.88-Tridecyl trifluoroacetate
4514.47-n-Cetane
4615.59-Farnesan
4716.10-Pyrogallol
4816.42-α-Copaene
4917.21-Caryophyllene
5017.35-Aromandendrene
5117.83-Dodecyliodide
5217.83-Heneicosane
5317.89-Alloarmadendrene
5418.04-γ-Muurolene
5518.08-Eicosane
5618.09-Tetracosane
5718.41-β-Bisabolene
5818.58-β-Chamigrene
5919.11-α-Calacorene
6019.50-Cetene
6119.83-Caryophyllene oxide
6219.83-α-Bulnesene
6320.13-Epiglobulol
6420.14-Ledol
6520.40-cis-Thujopsene
6620.69-Copaene
6721.15-Culmorin
6823.13-E-15-Heptadecenal
6923.48-cis-Z--Bisabolene epoxide
7027.27-Palmitic acid
7131.15-Stearic acid
7232.55-Hexachlorodisiloxane
7340.22-Squalene
7444.12-Vitamin E
7547.63-β-Sitosterol
Identified compounds from the ethyl acetate extract of P. guajava leaves
769.601-2-Isopropoxyethylamine[30]
7714.468-Bicyclo(7.2.0) undec-4-Ene,4,11,11-Trimethyl-8methylene-,[IR-(IR*,4Z,9S*)]-
7816.374-Caryophyllene
7916.754-Alpha-Farnesene
8016.874-Trans-Z,alpha-Bisaboleneepoxide
8117.804-Alpha-bisabolol
8219.850-Β-carotene
8322.116-Propanoic acid, 2-(Aminooxy)-
8425.948-2,4,6-Cycloheptatrien-1-one,3,5-Bis-Trimethylsilyl-
Identification of phytochemicals in guava leaf extract by GCMS
856:22.5-Caryophyllene[31]
865:55.80 α-Copaene
876:34.10 Cis-muurola-3,5-diene
886:35.80 Humulene
896:44.60 Cyclosativene
906:50.30 Bicyclo [5.3.0]decane, 2-methylene-5-(1methylvinyl)-8-methyl-
916:54.70 cis-à-Bisabolene
927:00.20 1H-Benzocycloheptene, 2,4a,5,6,7,8,9,9a-octahydro-3,5,5-trimethyl9-methylene-, (4aS-cis)-
937:08.90 1H-Cyclopropa[a] naphthalene,
1a,2,3,5,6,7,7a,7b-octahydro-1,1,7,7a-tetramethyl-,
[1aR-(1aà,7à,7aà,7bà)]
947:09.20 Naphthalene, 1,2,3,5,6,8a-hexahydro4,7-dimethyl-1-(1-methylethyl)-, (1S-cis)
957:12.80 Benzene, (1,3,3-trimethylnonyl)-
967:24.90 Cadala-1(10),3,8-triene
977:26.90 1,6,10-Dodecatrien-3-ol, 3,7,11-trimethyl-, (E)-
987:48.10 Spathulenol
997:46.60 Cubenol
1007:57.40 6S-2,3,8,8-Tetramethyltricyclo [5.2.2.0(1,6)]undec2-ene
1018:02.80 2-Hydroxy-2,4,4-trimethyl3-(3-methylbuta-1,3-dienyl)cyclohexanone
1028:04.40 Torreyol
1038:08.20 α-Cadinol
1048:09.20 5,6,6-Trimethyl-5-(3-oxobut1-enyl)-1-oxaspiro [2.5] octan-4-one
1058:13.30 α-Bisabolol
1069:28.10 Tetradecanoic acid, trimethylsilyl ester
1079:28.30 10-Undecynoic acid, trimethylsilyl ester
10811:00.30 Hexadecanoic acid, trimethylsilyl ester
10924:54.3 Isoamyllaurate
Table
Table 4. Phytochemicals identified from the leaf essential oil extracted from P. guajava.
Table 4. Phytochemicals identified from the leaf essential oil extracted from P. guajava.
Sr. No.CompoundRT (min)Area %References
Essential oil composition from leaf ofP. guajavafrom Kathmandu, Nepal.
1Limonene10280.17[32]
21,8-Cineole1031tr
3Benzyl alcohol10320.07
4Linalool11000.27
5trans-p-Mentha-2,8-dien-1-ol1120tr
6Chrysanthenone1124tr
7cis-p-Mentha-2,8-dien-1-ol1134tr
8trans-p-Menth-2-en-1-ol1139tr
9Terpinen-4-ol11760.11
10(3Z)-Hexenyl butanoate1187tr
11α-Terpineol11890.90
12Nerol12260.64
13(3Z)-Hexenyl 2-methylbutanoate1231tr
14Geraniol12521.48
15Methyl geranate1324tr
16Benzyl butanoate1346tr
17α-Cubebene13490.14
18Neryl acetate13650.17
19α-Copaene13752.82
20(3Z)-Hexenyl hexanoate1382tr
21Geranyl acetate13850.50
22β-Cubebene1390tr
23(E)-Caryophyllene141915.80
24cis-Muurola-3,5-diene14510.22
25α-Humulene14532.53
26allo-Aromadendrene14600.46
27Dauca-5,8-diene14740.18
28α-Amorphene14770.33
29Germacrene D1481tr
30trans-Muurola-4(14),5-diene14920.21
31epi-Cubebol14951.01
32α-Muurolene15010.30
33(Z)-α-Bisabolene15040.35
34β-Bisabolene15100.34
35Cubebol15161.30
36δ-Cadinene15254.03
37trans-Cadina-1,4-diene15331.44
38(E)-Nerolidol156935.59
39(3Z)-Hexenyl benzoate15730.28
40Caryophyllene oxide15842.59
41Gleenol15870.19
42Ledol16015.51
431,10-di-epi-Cubenol16160.27
441-epi-Cubenol16282.42
45Caryophylla-4(12),8(13)-dien-5-ol16360.41
46Cubenol16433.99
47α-Muurolol16463.05
48β-Eudesmol16510.34
49α-Cadinol16551.91
50epi-β-Bisabolol16710.39
51α-Bisabolol16860.12
52Shyobunol16900.46
53(2Z,6E)-Farnesol17236.70
Chemical Composition of Leaf Essential Oil of P. guajava L. from North East India
54α-Pinene5.480.33[33]
55Benzaldehyde6.160.33
56α-Myrcene6.320.53
57α-Terpinyl acetate7.1823.57
58p-Metha-trans-2,8-dien-1-ol8.810.09
59Citronella8.940.09
60cis-p-Menthe-1(7),8-dien-2-ol9.610.24
613-Cyclohexene-1-methanol, α, α-4-trimethyl-9.740.99
62Nerol10.050.28
63trans-p-Metha-1(7),8-dien-2-ol10.240.32
64α-Copaene12.496.50
65trans-Caryophyllene13.5517.65
66α-Humulene14.203.92
67γ-Muurolene14.480.73
68trans-α-bisabolene14.902.01
69(+)-e-Cadinene15.443.18
70cis-Calamenene15.601.97
71Naphthalene15.801.92
72Nerolidol16.4012.16
73Caryophyllene oxide17.093.66
74Ledol17.551.98
75Epiglobulol17.671.40
76iso-Aromadendrene epoxide17.962.55
77α-Cadinol18.336.71
78Viridiflorol18.632.38
79α-Cedrene19.170.38
80Ledeneoxide-(II)20.140.03
Phytochemicals indentifed from the leaf essential oil extracted from P. guajava by GC-FID and GC-MS from Lucknow India
81α-Pinene-0.8[35]
82Benzaldehyde-0.6
83β-Pinene-0.2
846-Methyl-5-hepten-2-one-t
85Myrcene-0.4
86α-Phellandrene-0.1
87p-Cymene-0.2
88Limonene-29.1
891,8-Cineole-2.6
90(Z)-β-Ocimene-t
91(E)-β-Ocimene-0.1
92γ-Terpinene-0.1
93Terpinolene-t
94Linalool-t
95Terpinen-4-ol-0.1
96α-Terpineol-0.5
97cis-Carveol-0.4
98Neryl acetate-0.1
99α-Copaene-2.3
100(E)-Caryophyllene-15.7
101α-Humulene-2.0
102allo-Aromadendrene-0.3
103γ-Muurolene-0.6
104Germacrene D-0.1
105Viridiflorene-1.2
106α-Selinene-1.3
107α-Muurolene-t
108(Z)-α-Bisabolene-t
109β-Bisabolene-0.3
110γ-Cadinene-0.2
111δ-Cadinene-1.7
112trans-Cadina-1,4-diene-0.5
113α-Calacorene-0.1
114(E)-Nerolidol-4.0
115Caryophyllenyl alcohol-0.3
116Caryophyllene oxide-8.8
117Gleenol-0.1
118Ledol-0.2
119Humulene epoxide II-1.3
1201-epi-Cubenol-0.2
121Muurola-4,10(14)-dien-1-β-ol-2.5
122Caryophylla-4(12),8(13)-dien-5-ol-6.5
123epi-α-Muurolol-t
124α-Muurolol-1.1
125α-Cadinol-3.4
126(2Z,6E)-Farnesol-0.9
Table
Table 5. Antioxidant and anticancer activities of isolated compounds from P. guajava L.
Table 5. Antioxidant and anticancer activities of isolated compounds from P. guajava L.
Test CompoundsAntioxidantAnticancerReferences
Guavinoside A (1)DPPH = IC50 37.93 ± 0.50 µg/mL, ABTS = IC50 13.63 ± 1.25 µg/mL, FRAP = IC50 (12.5 µg/mL) 18.46 ± 7.50, IC50 (25 µg/mL) 53.29 ± 16.84, IC50 (50 µg/mL) 131.03 ± 21.31, IC50 (100 µg/mL) 174.60 ± 16.36SGC = >10, A549 = > 10, Hela = > 10[36]
Guavinoside B (2)DPPH = IC50 8.30 ± 1.35 µg/mL, ABTS = IC50 5.47 ± 0.65 µg/mL, FRAP = IC50 (12.5 µg/mL) 48.30 ± 10.71, IC50 (25 µg/mL) 90.63 ± 8.10, IC50 (50 µg/mL) 185.03 ± 19.38, IC50 (100 µg/mL) 341.94 ± 12.90SGC = >10, A549 = > 10, Hela = > 10
Guavinoside C (3)DPPH = IC50 13.07 ± 0.57 µg/mL, ABTS = IC50 5.47 ± 0.65 µg/mL, FRAP = IC50 (12.5 µg/mL) 91.28 ± 12.92, IC50 (25 µg/mL) 143.76 ± 28.44, IC50 (50 µg/mL) 250.53 ± 24.02, IC50 (100 µg/mL) 386.38 ± 25.31SGC = IC50 4.277 µg/mL, A549 = IC50 7.288 µg/mL, Hela = IC50 3.246 µg/mL
Guavinoside D (4)DPPH = IC50 > 100 µg/mL, ABTS = IC50 29.27 ± 0.67 µg/mL, FRAP = IC50 (12.5 µg/mL) ND, IC50 (25 µg/mL) ND, IC50 (50 µg/mL) ND, IC50 (100 µg/mL) NDSGC = > 10, A549 = > 10, Hela = > 10
Guavinoside E (5)DPPH = IC50 >100 µg/mL, ABTS = IC50 32.97 ± 3.5 µg/mL, FRAP = IC50 (12.5 µg/mL) 11.54 ± 1.33, IC50 (25 µg/mL) 14.00 ± 4.43, IC50 (50 µg/mL) 23.73 ± 3.73, IC50 (100 µg/mL) 46.37 ± 1.27SGC = > 10, A549 = > 10, Hela = > 10
Guavinoside F (6)DPPH = IC50 13.10 ± 0.10 µg/mL, ABTS = IC50 5.93 ± 0.21 µg/mL, FRAP = IC50 (12.5 µg/mL) 70.64 ± 16.29, IC50 (25 µg/mL) 152.02 ± 13.98, IC50 (50 µg/mL) 263.31 ± 14.12, IC50 (100 µg/mL) 413.94 ± 14.36SGC = IC50 4.277 µg/mL, A549 = IC50 7.288 µg/mL, Hela = IC50 3.246 µg/mL
guajanoside A (7)DPPH = IC50 131.87 ± 4.12 μM [37]
guajanoside B (8)DPPH = IC50 113.33 ± 3.44 μM
guajanoside C (9)DPPH = IC50 114.94 ± 3.19 μM
guajanoside D (10)DPPH = IC50 97.68 ± 1.88 μM
guajanoside E (11)DPPH = IC50 97.05 ± 7.83 μM
cypellocarpin C (12)DPPH = IC50 > 200 μM
eucamalduside A (13)DPPH = IC50 180.00 ± 3.57μM
cypellogin A (14)DPPH = IC50 103.95 ± 0.06 μM
cypellogin B (15)DPPH = IC50 98.75 ± 1.22 μM
quercetin-3-O-β-
d-(6″-O-p-coumaroyl)-galactopyranoside (16)		DPPH = IC50 92.55 ± 4.03μM
Guavaric A (17)DPPH = IC50 84.28 ± 4.68 μM
3,5-dihydroxy-2,4-
dimethyl-1-O-(6′-O-galloyl-β- d -glucopyranosyl)-benzophenone (18)		 HCT116 = at 40 μM by 1.50-fold (3.65%), at 60 by 2.33-fold (5.67%), at 80 μM by
10.08-fold (24.53%)		[38]
quercetin (19)FRAP = IC50 (12.5 µg/mL) 333.26 ± 1.76, IC50 (25 µg/mL) 359.18 ± 15.14, IC50 (50 µg/mL) 379.40 ± 10.31, IC50 (100 µg/mL) 401.27 ± 12.23 [36]
quercetin-3-O-a- L -arabino-
furanoside (20)		FRAP = IC50 (12.5 µg/mL) 123.88 ± 14.95, IC50 (25 µg/mL) 269.00 ± 7.28, IC50 (50 µg/mL) 291.63 ± 32.79, IC50 (100 µg/mL) 324.58 ± 10.64
quercetin-3-O-a- l -arabinopyranoside (21)FRAP = IC50 (12.5 µg/mL) 57.21 ± 4.94, IC50 (25 µg/mL) 175.59 ± 7.11, IC50 (50 µg/mL) 220.51 ± 22.18, IC50 (100 µg/mL) 346.45 ± 25.61
querce-
tin-3-O-b- D -galactopyranoside (22)		FRAP = IC50 (12.5 µg/mL) 68.06 ± 5.74, IC50 (25 µg/mL) 155.89 ± 17.90, IC50 (50 µg/mL) 287.94 ± 2.26, IC50 (100 µg/mL) 329.68 ± 17.72
Guajavadimer A (23)-HepG2 = OD (mean ± SD) 1.654 ± 0.094[39]
Psiguajavadial A (24)-HCT116 = IC50 7.60 µM, CCRF-CEM = IC50 25.2 µM, DU145 = IC50 20.2 µM, Huh7 = IC50 48.8 µM, A549 = IC50 2.99 µM[40,41,42,43,44,45,46,47,48,49]
Psiguajavadial B (25) HCT116 = IC50 21.6 µM; CCRF-CEM = IC50 9.63 µM; DU145 = IC50 26.3 µM; Huh7 = IC50 13.7 µM; A549 = IC50 0.90 µM
Guadial A (26) HCT116 = IC50 5.74 µM; CCRF-CEM = IC50 2.95 µM; DU145 = IC50 5.35 µM; Huh7 = IC50 28.0 µM; A549 = IC50 9.62 µM
Guadial B (27) HCT116 = IC50 26.5 µM; CCRF-CEM = IC50 6.72 µM; DU145 = IC50 18.0 µM; Huh7 = IC50 55.3 µM; A549 = IC50 13.4 µM
Guadial C (28) HCT116 = IC50 13.0 µM; CCRF-CEM = IC50 12.9 µM; DU145 = IC50 14.5 µM; Huh7 = IC50 29.6 µM; A549 = IC50 5.70 µM
Psiguadial B (29) HCT116 = IC50 15.5 µM; CCRF-CEM = IC50 18.2 µM; DU145 = IC50 43.3 µM; Huh7 = IC50 47.0 µM; A549 = IC50 8.73 µM
Psiguadial C (30) HCT116 = IC50 14.4 µM; CCRF-CEM = IC50 9.3 µM; DU145 = IC50 49.1 µM; Huh7 = IC50 10.8 µM; A549 = IC50 3.06 µM
Psiguadial D (31) HCT116 = IC50 7.0 µM; CCRF-CEM = IC50 2.59 µM; DU145 = IC50 6.08 µM; Huh7 = IC50 5.20 µM; A549 = IC50 1.07 µM
Guajadial (32) HCT116 = IC50 20.4 µM; CCRF-CEM = IC50 0.87 µM; DU145 = IC50 11.8 µM; Huh7 = IC50 20.7 µM; A549 = IC50 2.42 µM
Psidial A (33) HCT116 = IC50 11.5 µM; CCRF-CEM = IC50 17.4 µM; DU145 = IC50 11.9 µM; Huh7 = IC50 47.0 µM; A549 = IC50 14.1 µM
4,5-diepipsidial A (34) HCT116 = IC50 9.13 µM; CCRF-CEM = IC50 7.0 µM; DU145 = IC50 4.79 µM; Huh7 = IC50 2.82 µM; A549 = IC50 0.16 µM
Guajadial B (35) HCT116 = IC50 3.54 µM; CCRF-CEM = IC50 7.58 µM; DU145 = IC50 16.4 µM; Huh7 = IC50 2.93 µM; A549 = IC50 0.15 µM
Guajadial C (36) HCT116 = IC50 4.42 µM; CCRF-CEM = IC50 42.8 µM; DU145 = IC50 55.4 µM; Huh7 = IC50 2.93 µM; A549 = IC50 33.6 µM
Guajadial D (37) HCT116 = IC50 0.61 µM; CCRF-CEM = IC50 16.0 µM; DU145 = IC50 30.3 µM; Huh7 = IC50 44.09 µM; A549 = IC50 36.2 µM
Guajadial E (38) HCT116 = IC50 4.69 µM; CCRF-CEM = IC50 12.7 µM; DU145 = IC50 23.2 µM; Huh7 = IC50 51.5 µM; A549 = IC50 18.4 µM
Guajadial F (39) HCT116 = IC50 3.66 µM; CCRF-CEM = IC50 7.80 µM; DU145 = IC50 27.7 µM; Huh7 = IC50 11.1 µM; A549 = IC50 13.8 µM
Guajavadial A (40) HL-60 = IC50 4.73 µM; A-549 = IC50 5.62 µM; SMMC-7721 = IC50 4.37 µM; MCF-7 = IC50 22.28 µM; SW480 = IC50 14.55 µM[50]
Guajavadial B (41) HL-60 = IC50 6.49 µM; A-549 = IC50 5.78 µM; SMMC-7721 = IC50 5.05 µM; MCF-7 = IC50 18.02 µM; SW480 = IC50 13.07 µM
Guajavadial C (42) HL-60 = IC50 3.38 µM; A-549 = IC50 5.66 µM; SMMC-7721 = IC50 3.54 µM; MCF-7 = IC50 14.54 µM; SW480 = IC50 18.97 µM
Psiguajadial A (43) [41,44,47,51]
Psiguajadial B (44)
Psiguajadial C (45)
Psiguajadial D (46)
Psiguajadial E (47)
Psiguajadial F (48)
Psiguajadial G (49)
Psiguajadial H (50)
Psiguajadial I (51)
Psiguajadial J (52)
Psiguajadial K (53)
Psiguadial A (54)
Guapsidial A (55) HepG2 = IC50 45.93 ± 6.83 μM, Hela = IC50 39.33 ± 6.21 μM
Psiguajadial L (56)
Psiguajdianone (58) HepG2 = IC50 27.90 ± 0.85 μM, Hela = IC50 28.14 ± 2.79 μM[52]
Psiguajanone A (59)
Psiguajanone B (60)
Psiguajanone C (61) HepG2 = IC50 27.45 ± 2.32 μM
Psiguajanone D (62)
Psiguajanol A (63)
Psiguadiols A (64) [53]
Psiguadiols G (70)
Psiguadiols H (71)
psiguamers A ((+)74) HCT-116 = IC50 2.94 μmol/L, HepG2 = IC50 9.01 μmol/L, BGC-823 = IC50 6.45 μmol/L, A549 = IC50 5.42 μmol/L, and U251 = IC50 5.33 μmol/L[54]
Table
Table 6. Anti-inflammatory and Enzyme inhibitory activities of isolated compounds from P. guajava L.
Table 6. Anti-inflammatory and Enzyme inhibitory activities of isolated compounds from P. guajava L.
Test CompoundsAnti-InflammatoryEnzyme InhibitoryReferences
Guadial A (26) PDE4D-4 = IC50 2.70 μM
Guajadial (32) PDE4D-4 = IC50 1.62 μM
Guajadial C (36) PDE4D-4 = IC50 2.28 μM
Guajadial D (37) PDE4D-4 = IC50 1.93 μM
Guajadial E (38) PDE4D-4 = IC50 2.73 μM
Guajadial F (39) PDE4D-4 = IC50 2.67 μM
Guajavadial A (40) PDE4D-4 = IC50 2.01 μM[50]
Psiguajadial A (43) PDE4D-4 = IC50 3.11 μM[41,44,47,51]
Psiguajadial B (44) PDE4D-4 = IC50 5.03 μM
Psiguajadial C (45) PDE4D-4 = IC50 4.50 μM
Psiguajadial D (46)NO = IC50 11.82 ± 1.17 μM, TNF-α = IC50 31.59 ± 3.18 μM, PEG2 = IC50 13.63 ± 0.59 μMPDE4D-4 = IC50 4.14 μM
Psiguajadial E (47) PDE4D-4 = IC50 3.25 μM
Psiguajadial F (48) PDE4D-4 = IC50 2.63 μM
Psiguajadial G (49) PDE4D-4 = IC50 1.34 μM
Psiguajadial H (50) PDE4D-4 = IC50 1.81 μM
Psiguajadial I (51) PDE4D-4 = IC50 2.51 μM
Psiguajadial J (52) PDE4D-4 = IC50 2.53 μM
Psiguajadial K (53) PDE4D-4 = IC50 3.68 μM
Psiguadial A (54) PDE4D-4 = IC50 7.26 μM
Guapsidial A (55)NO = IC50 11.15 ± 0.42 μM, TNF-α = IC50 37.64 ± 3.83 μM, PEG2 = IC50 15.38 ± 0.39 μMPDE4D-4 = IC50 5.61 μM
Psiguajadial L (56) PDE4D-4 = IC50 1.37 μM
Psiguajdianone (58)NO = IC50 9.07 ± 0.27 μM, TNF-α = IC50 12.57 ± 0.56 μM, PEG2 = IC50 4.27 ± 0.55 μM [52]
Psiguajanone A (59)NO = IC50 6.11 ± 0.09 μM, TNF-α = IC50 1.88 ± 0.83 μM, PEG2 = IC50 6.36 ± 1.27 μM
Psiguajanone B (60)NO = IC50 5.72 ± 1.19 μM, TNF-α = IC50 2.10 ± 0.72 μM, PEG2 = IC50 4.00 ± 0.74 μM
Psiguajanone C (61)NO = IC50 4.36 ± 0.36 μM, TNF-α = IC50 5.97 ± 1.52 μM, PEG2 = IC50 2.24 ± 0.65μM
Psiguajanone D (62)NO = IC50 7.38 ± 2.60 μM, TNF-α = IC50 1.66 ± 0.26 μM, PEG2 = IC502.09 ± 0.06 μM
Psiguajanol A (63)NO = IC50 2.86 ± 0.95μM, TNF-α = IC50 5.28 ± 1.56 μM, PEG2 = IC50 1.08 ± 0.08 μM
Psiguadiols A (64) PTP1B = IC50 4.7 μM,[53]
Psiguadiols G (70) PTP1B = IC50 6.2 μM,
Psiguadiols H (71) PTP1B = IC50 9.2 μM,
psiguamers A ((+)74) [54]
Jejuguajavones A (88) PTP1B = IC50 10.52 ± 0.71 μM,[55]
Jejuguajavones B (89) PTP1B = IC50 37.83 ± 3.54 μM,
Jejuguajavones C (90) PTP1B = IC50 9.40 ± 0.76 μM,
Jejuguajavones D (91) PTP1B = IC50 35.94 ± 4.73 μM,
Table
Table 9. Minimal inhibitory concentration (MIC) values of P. guajava leaves extract.
Table 9. Minimal inhibitory concentration (MIC) values of P. guajava leaves extract.
Tested MicroorganismsMethanolEthanolAcetoneEthyl AcetateHot Water
S. aureus10.3 ± 0.58 Da16.7 ± 1.15 Db29.3 ± 0.58 Ca41.7 ± 1.53 Ca7.0 ± 0.00 Db
L. monocytogenes8.3 ± 0.58 Da16.7 ± 1.15 Da14.3 ± 3.06 Da66.7 ± 5.8 Ba5.0 ± 0.00 Da
B. cereus10.3 ± 0.58 Da20.7 ± 1.52 Db12.3 ± 0.58 Da116.7 ± 15.28 Aa6.0 ± 0.00 Da
S. typhmurium5.0 ± 0.00 Db20.7 ± 1.52 Db10.3 ± 0.58 Db83.3 ± 2.89 Bc13.3 ± 0.58 Db
E. coli O:1577.3 ± 0.58 Db25.0 ± 0.00 Cb14.3 ± 3.06 Db100.0 ± 0.00 Ab14.3 ± 0.58 Db
P. mirabilis5.0 ± 0.00 Db20.7 ± 1.52 Db10.3 ± 0.58 Db116.7 ± 15.28 Ac13.3 ± 0.58 Db
P. aeruginosa8.3 ± 0.58 Db20.7 ± 1.52 Db8.3 ± 0.58 Db116.7 ± 15.28 Ac14.3 ± 0.58 Db
K. pneumoniae14.3 ± 3.06 Db29.3 ± 0.58 Ca10.3 ± 0.58 Db83.3 ± 2.89 Bb16.7 ± 1.15 Db
Figures having same capital letters and small letters are significantly different at p = 0.05 probability by Fisher’s PLSD test. LSD 0.05 solvent 0.05 solvent 18.089, plant part 12.202.
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Tousif, M.I.; Nazir, M.; Saleem, M.; Tauseef, S.; Shafiq, N.; Hassan, L.; Hussian, H.; Montesano, D.; Naviglio, D.; Zengin, G.; et al. Psidium guajava L. An Incalculable but Underexplored Food Crop: Its Phytochemistry, Ethnopharmacology, and Industrial Applications. Molecules 2022, 27, 7016. https://doi.org/10.3390/molecules27207016

AMA Style

Tousif MI, Nazir M, Saleem M, Tauseef S, Shafiq N, Hassan L, Hussian H, Montesano D, Naviglio D, Zengin G, et al. Psidium guajava L. An Incalculable but Underexplored Food Crop: Its Phytochemistry, Ethnopharmacology, and Industrial Applications. Molecules. 2022; 27(20):7016. https://doi.org/10.3390/molecules27207016

Chicago/Turabian Style

Tousif, Muhammad Imran, Mamona Nazir, Muhammad Saleem, Saba Tauseef, Nusrat Shafiq, Laiba Hassan, Hidayat Hussian, Domenico Montesano, Daniele Naviglio, Gokhan Zengin, and et al. 2022. "Psidium guajava L. An Incalculable but Underexplored Food Crop: Its Phytochemistry, Ethnopharmacology, and Industrial Applications" Molecules 27, no. 20: 7016. https://doi.org/10.3390/molecules27207016

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