Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
3. Carica papaya Counteracts Oxidative Stress in Inflammation, Skin Aging, and Healing, Chronic Diseases, and Cancers
3.1. Inflammation
3.2. Diabetes
3.3. Alzheimer’s Disease (AD)
3.4. Periodontal Disease
3.5. Skin Aging
3.6. Wound Healing
Part of the Plant | Extract | Type of Experiment | Results | Reference |
---|---|---|---|---|
Seed | Aqueous extract | In vitro cytoprotective assay | Aqueous extract of papaya seeds at 1mg/mL showed cytoprotective against H2O2 induced cell toxicity. | [61] |
Cell apoptosis assay | Aqueous extract of papaya seeds at a concentration of 1 mg/mL inhibited H2O2 induced apoptosis by approximately 30%. | |||
MMP and Cytochrome C assay | Seed extract at 1 mg/mL inhibited oxidative stress-induced cell apoptosis, reduced mitochondrial dysfunction and impeded release of cytochrome C. | |||
Western blot analysis | 1 mg/mL of seed extract decreased overexpression of HSP-70 in fibroblasts. | |||
- | Fermented papaya (Biorex) | In vitro HRBC model | Biorex inhibited superoxide (IC50 = 5 mg/mL), hydroxyl radicals (IC50 = 1.1 mg/mL), and total ROS (IC50 = 2 mg/mL) in human red blood cells. | [62] |
In vitro animal model | Biorex (1–5 mg/mL) decreased the elevated radical generation in rats with burn trauma. Biorex reduced local inflammation and catalase activity. | |||
Unripe pulp | Papaya extract +/− Selenium | In vitro animal model | Papaya extract alone (PE) or with selenium (PES) enhanced wound closure in rats. Both PE and PES augmented SOD, CAT, and GPx activities. PE with selenium ameliorated oxidative damage at the wound site. PE enhanced wound healing via attenuating excessive inflammation, reduced COX-2, and MPO enzyme activity. PE and PES increased NO content by increasing iNOS, stimulating collagen deposition and angiogenesis. PE suppressed arginase activity during wound healing as indicated by decreased wound urea content. | [63] |
Unripe papaya pulp | Papaya aqueous extract. Or Papaya PBS extract + Selenium | In vitro animal model | Total protein content (95.14 ± 1.15 mg/g tissue) in wound tissue was significantly higher in rats treated with PES at a dose 5 mg/mL twice daily for papaya and 0.5 μg/20 mL for selenium. Rats treated with PES demonstrated elevation in wound hydroxyproline (*55.15 ± 1.06 μg/mg), hexuronic acid (*60.84 ± 6.08 mg/g), and hexosamine (*35.23 ± 4.95 mg/g) contents. Overall reduced in migration of polymorphonuclear monocytes and increased fibroblast recruitment at wound sites. PE enhanced collagen synthesis and vascularization. Time required for wound closure was shortened, indicated by earlier increment in VEGFA and TGF-β1 expression. | [64] |
- | FPP | In vitro animal model | FPP at a dose of 200 mg/kg s improved wound closure via increasing ROS (superoxides) production by macrophages at wound site and promoting NO production at ~60%. Increased NO and ROS to support redox signaling and angiogenesis. FPP increased CD68, VEGF transcription, macrophages recruitment to wound site and promoted optimal angiogenesis environment. | [65] |
Leaf | Aqueous extract | In vitro animal model | Aqueous extract of papaya leaves at a dose of 500 mg/kg protected the stomach from absolute ethanol induced injury. Aqueous extract decreased MDA levels by 0.031 μmol/L and increased GPx by 0.246 U/mg protein. | [68] |
Fruit | Aqueous extract | In vitro animal model | Aqueous extract of papaya fruit significantly shrank the wound area at 100 mg/kg by 77% by increasing epithelialization rate, weight of dry and wet granulation tissues and promoting enzymatic debridement of wound. Aqueous extract-treated wound showed rapid collagen turnover and accumulation that enhanced wound healing. | [69] |
Tree | Dried latex incorporated into hydrogel | In vitro animal model | Topical application of the dried latex-containing hydrogel (1–2.5%) increased hydroxyproline content. Significant wound contraction after application of this hydrogel day 12 at concentration of 2.5% and on day 20 at both concentrations of 1.0% and 2.5%. | [70] |
Seed | Ethanol extract | In vitro animal model | Ethanol extract of papaya seeds at a dose of 50 mg/kg significantly reduced wound area by 88.96%. Ethanol extract produces well-organized collagen deposition and significant fibroblast activity. | [71] |
3.7. Cancers
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Part of the Plant | Extract | Type of Experiment | Results | Reference |
---|---|---|---|---|
Seed | Aqueous extract | In vitro cell free model In vitro HRBC assay | Aqueous extract of papaya seeds at 20 μg/mL decreased NO radical by 69.4%, comparable to ascorbic acid. | [15] |
Aqueous extract of papaya seeds at 150 μg/mL inhibited the release of lysosomal enzyme by 22.7%. | ||||
Leaf | Leaf extract | In vitro animal model | Leaf extract at 1.32 μg/mL enhanced adaptive immune response by upregulated TLR-7 and TLR-9 expressions. | [17] |
Fruit (ripe, unripe fruit, peel, seed, pulp) | Aqueous extract | In vitro ROS assay | Unripe peel (69.7%) and seed (79.1%) extract at 2mg/mL showed ROS scavenging activity of 69.7 and 79.1% at 2 mg dry weight/mL. | [18] |
In vitro antioxidant enzyme assay | Aqueous extract of papaya unripe peel at 2 mg dry weight/mL increased SOD activity by 21.9%. | |||
In vitro protein carbonyl assay | Aqueous extract reduced oxidative damage by lowered protein carbonyl production for ripe seed (60.4%) and ripe peel (57.6%) extract at 0.1 and 2 mg/mL. | |||
In vitro inflammatory cytokines assay | The extracts augmented IL-10 levels at a low concentration of 0.1 mg/mL. Seed extracts exerted highest increment in IL-10 secretory level (+140.1%), followed by peel and pulp extracts. Seed extracts at 0.1 mg dry weight/mL exerted increment in IL-10 secretory level (+140.1%). | |||
Aqueous extract of papaya seeds at 2 mg dry weight/mL down regulated IL-6 by 37.8%. | ||||
Unripe extracts at 2 mg/mL showed inhibitory activity against TNF-α with 71.2% for pulp extract, 62.7% for peel and 65.3% for seed extract. | ||||
Fruit (Flesh) | Juice | In vitro animal model | Papaya juice downregulated the elevated serum IL-6 (217.6 vs. 28.3 pg/dL) and MDA (3.2 vs.1.4 pg/dL) in high fat diets treated rats. Papaya juice affected serum SOD of the high fat treated rat by increased serum SOD (30.41 U/L). | [19] |
Leaf | Ethanol extract | In vitro animal model | Ethanol extract of papaya leaves at 200 mg/kg reduced paw edema (2.6 mm) and inhibited granuloma formation (0.2 g). | [20] |
Part of the Plant | Extract | Type of Experiment | Results | Reference |
---|---|---|---|---|
Seed | Hexane extract & ethyl acetate extract | In vitro DPPH radical scavenging assay | Hexane extract possessed DPPH radical scavenging activity with IC50 = 41.5 mg/mL. | [27] |
In vitro TBA method | Hexane extract demonstrated TBA scavenging activity with IC50 = 38.2 mg/mL. | |||
In vitro α-glucosidase inhibition | Hexane extract displayed α-glucosidase enzyme inhibitory activity with IC50 = 75.78 mg/mL. | |||
Ethyl acetate extract exhibited α-glucosidase enzyme inhibitory activity with IC50 = 77.41 mg/mL. | ||||
In vitro α-amylase inhibition | Hexane extract demonstrated α-amylase inhibitory activity with IC50 = 76.96 mg/mL. | |||
Ethyl acetate extract displayed α-amylase inhibitory activity with IC50 = 79.18 mg/mL. | ||||
In vitro FRAP assay | Ethyl acetate extract displayed FRAP inhibitory activity with IC50 = 38.75 mg/mL. | |||
In vitro animal model | Ethyl acetate extract at 500 mg/kg/body weight significantly decreased the blood glucose level of the diabetic rats to approximately 120 mmol/L over 120 min comparable with standard drug, acarbose. | |||
- | FPP | In vitro analysis | FPP at concentration 50 μg/mL increased inner and outer platelet membrane fluidity, displayed by a decrease of ~0.015 r in DPH anisotropy and ~0.02 r in TMA-DPH anisotropy. FPP increased Naþ/Kþ-ATPase activity by ~0.5 μmol Pi/mg prot/h.-FPP improved platelet function in vitro and this might help preventing diabetic complications. FPP also slightly increased TAC by ~5 nmol/μL and SOD activity by ~0.5 units/μL. FPP at 50 μg/mL lowered lipid peroxidation. | [28] |
- | FPP® | Human trial | FPP significantly improved liver sensitivity to insulin, which was indicated by decreased circulating AST and ALT. FPP scavenged NO and hydroxyl radicals and displayed an increased in total antioxidant status. | [29] |
- | FPP | In vitro DPPH radical scavenging assay | FPP displayed DPPH scavenging with AA50 = 55.69 mg/mL. | [30] |
In vitro ABTS+ scavenging assay | FPP demonstrated ABTS+ scavenging action with AA50 = 14.56 mg/mL. | |||
In vitro AAPH-induced lipid oxidation inhibition | FPP inhibited AAPH-induced lipid oxidation with AA50 = 68.06 mg/mL. | |||
In vitro O2− scavenging assay | FPP showed O2− scavenging action with AA50 = 88.70 mg/mL. | |||
In vitro •OH scavenging assay | FPP showed hydroxyl radical scavenging activity with AA50 = 4.13 mg/mL. | |||
Human trial | FPP at a dose of 6g/day showed an increase of 4.9% and 5.7% in TAS for male and female respectively after 14-week consumption at 6g/day. FPP decreased protein carbonyl level by 1.9% in males and 9.7% in females after a 14-week FPP ingestion. FPP delayed red blood cell hemolysis. | |||
Seed, flesh and peel of unripe fruit | Aqueous extract | In vitro α-amylase inhibition In vitro α-glucosidase inhibition In vitro lipid peroxidation assay In vitro NO scavenging assay | Aqueous extract inhibited α-glucosidase and α-amylase activities with IC50 of 1.76 mg/mL and IC50: 0.87 mg/mL. At a concentration of 7.5 mg/mL, the extract also displayed the highest NO radical scavenging activity (52.5%). | [31] |
Leaf | Chloroform extract | In vitro animal model | The chloroform extract at a dose of 31 mg/kg/day significantly increased islet area by 16,842.2 μm2 by stimulating regeneration of β-cells of islet of Langerhans. | [32] |
The extract successfully decreased fasting glucose levels by 222.3 mg/dL in diabetic group in vivo. | ||||
Leaf | Aqueous extract | In vitro animal model | Aqueous extract at a dose of 3 g/100 mL decreased blood glucose levels in diabetic rats by 184 mg/dL. Aqueous extract at a dose of 1.5 g/100 mL preserved Islet cell size in diabetic rats. Aqueous extract increased NO levels by 17.39 μM and hence reduced ROS production. | [33] |
Part of the Plant | Extract | Type of Experiment | Results | Reference |
---|---|---|---|---|
Unripe papaya juice | In vitro antioxidant enzyme assays | Papaya juice at 1 mg/mL enhanced SOD (49%) and CAT (40.5%) activities. | [45] | |
Western blot analysis | Papaya juice at 1 mg/mL restrained NF-κB translocation to nuclei and downregulated Nrf2 levels. | |||
Leaf | Ethanol extract | In vitro DPPH assay | Ethanol extract at 250 μg/mL showed ROS scavenging effect at 60%. | [47] |
In vitro DCFH-DA assay | Ethanol extract at 50 μg/mL showed potent suppressing action towards UVB-induced ROS production (60%). | |||
In vitro MMPs and inflammatory cytokines production | Ethanol extract at 50 μg/mL of Carica papaya leaves enhances synthesis and prevents degradation of type I collagen via upregulating TGF-β1 and down-regulating MMP-1 (34% at 50 μg/mL), MMP-3, and IL-6 generation. Ethanol extract at 50 μg/mL of Carica papaya leaves reduced mRNA level of MMP-1 (56.8%) and type I procollagen (288.8%). | |||
Western blotting assay | Ethanol extract at 50 µg/mL showed AP-1 activation via down-regulating c-Fos (89%) and c-Jun (44%) phosphorylation. Ethanol extract at 50 µg/mL attenuated MAPK activation, and p38 phosphorylation (82%), followed by ERK, and JNK phosphorylation. | |||
FPP | Double-blinded RCT | FPP at a dose of 4.5 g showed anti-skin aging by demonstrating overall higher skin moisturization, elasticity, and surface evenness. FPP at a 4.5 g inhibited MDA production and up modulation of AQP-3, enhanced SOD and NO levels in FPP-treated group. FPP at 4.5 g downregulated pro-aging factors (CyPA and CD147 genes) suggesting to reduce risk of skin carcinogenesis. | [48] |
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Kong, Y.R.; Jong, Y.X.; Balakrishnan, M.; Bok, Z.K.; Weng, J.K.K.; Tay, K.C.; Goh, B.H.; Ong, Y.S.; Chan, K.G.; Lee, L.H.; et al. Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review. Biology 2021, 10, 287. https://doi.org/10.3390/biology10040287
Kong YR, Jong YX, Balakrishnan M, Bok ZK, Weng JKK, Tay KC, Goh BH, Ong YS, Chan KG, Lee LH, et al. Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review. Biology. 2021; 10(4):287. https://doi.org/10.3390/biology10040287
Chicago/Turabian StyleKong, Yew Rong, Yong Xin Jong, Manisha Balakrishnan, Zhui Ken Bok, Janice Kwan Kah Weng, Kai Ching Tay, Bey Hing Goh, Yong Sze Ong, Kok Gan Chan, Learn Han Lee, and et al. 2021. "Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review" Biology 10, no. 4: 287. https://doi.org/10.3390/biology10040287