Exhaustive Plant Proﬁle of “ Dimocarpus longan Lour” with Signiﬁcant Phytomedicinal Properties: A Literature Based-Review

: Background: “ Dimocarpus longan Lour” is a tropical and subtropical evergreen considered an alternative source of medication for some diseases as it contains a potential group of chemical constituents. cm) long, held on the panicle in bunch form [3]. Dimocarpus longan fruits are small and drupaceous fruit of 22–36 mm in diameter and weight of 6–19 g. Heart-shaped longan fruits contain only one seed, and fruits are mostly yellowish to light brown with melliﬂuous carriage peel. The edible portion is robust with fettle white-peel; furthermore, 350 fruits may be carried by panicles and ﬂowering to harvest is from 140–190 days [3]. Hence, mature longan fruit contains one seed inside the fruit; basically, the seed is orbicular with black or brown color with a rounded white spot that has the appearance of a dragon’s eye [51]. Various parts of this part are graphically represented under the Figure 1.

China is the original birthplace of the longan tree, but it is widespread in all parts of South Asian countries. All tropical and sub-tropical countries produce this tree, but it is mainly propagated in China and Thailand [45]. It is noteworthy that different countries commercially cultivate this tree, for example, China, Thailand, India, and Vietnam [46]. Counter-wise, Crane et al. (2005) [3] reported that the tree was found in Taiwan, Myanmar, Cambodia, Laos, Australia, Kenya, some Central and South American countries, and southern African countries. In Bangladesh, the district of Barisal is most famous for cultivating the Dimocarpus longan Lour and it is known locally as "Kath litchi or Ashphal", which is used as an edible fruit as well as for medicinal purposes (mainly used as an antidote) [47].

Complete Botanical Description of D. longan tree
The longan is a very gracious, vertical, and static tree with 20 m height and diameter depending on climate and soil conditions. The orbicular shape at the top of the tree grows with uneven and mercurial peel [48]. Evergreen leaves of the longan tree are dilated with 6-9 leaflets per pair of spare and paripinnate leaves. The leaves are up to 30 cm (12 inches) long and 3.5-5 cm wide with deep margins and stingless tops of the leaves. However, the longan tree forms shiny leaves with dark green on the upper sides and on the lower base the leaves have a mild green color. Leaves are usually smooth but now and then they have a woolly texture [49]. A longan tree usually forms one shoot per year, but sometimes it produces more than one flurry of the shoot and the tree shoots over summer or autumn. Moreover, flowers are small, just 5-6 petalled and the tree produces both unisexual and bisexual (hermaphroditic) flowers [50]. The petals of these flowers are yellow-brown with the tree bearing flowers towards the end of winter. Besides, the female flower conveys a carpellate ovary; flowers are 4-18 inches (10-45 cm) long, held on the panicle in bunch form [3]. Dimocarpus longan fruits are small and drupaceous fruit of 22-36 mm in diameter and weight of 6-19 g. Heart-shaped longan fruits contain only one seed, and fruits are mostly yellowish to light brown with mellifluous carriage peel. The edible portion is robust with fettle white-peel; furthermore, 350 fruits may be carried by panicles and flowering to harvest is from 140-190 days [3]. Hence, mature longan fruit contains one seed inside the fruit; basically, the seed is orbicular with black or brown color with a rounded white spot that has the appearance of a dragon's eye [51]. Various parts of this part are graphically represented under the Figure 1.

Ethnobotanical Usages of longan
In China, the pulp of the longan Lour fruit showed diverse effective health biological functions, for instance, flourishing blood metabolism, calming and relaxing nerves, alleviating insomnia, restraining amnesia, enhancing longevity, relieving nerve pain, curing nerve swelling, and medicating palpitations [14]. Additionally, for a long time, the longan plant was used to treat fatigue diseases. The phytochemical constituents of the flowers and seeds of longan decrease the pain associated with urinary disorders. However, the flower, root, pulp, and pericarp have antioxidant, anti-glycation, anti-tyrosinase, anti-fungal, anti-microbial, and anti-cancerous activities. For these reasons, these parts are used in medication for diabetes, cancer, fungal, microbial infections, etc. [14,49]. In Bangladesh, the local "kaviraj" in Barisal use it for different diseases, such as gastrointestinal disorders, cuts and wounds, fever, snake bites, menstrual problems, chickenpox, bone fractures, cattle disorders, and so on; it is more prevalently used as the antidote for poison [47]. In Tabgail, longan is used locally to treat neurological disorders and reproductive health [52].

Ethnobotanical Usages of Longan
In China, the pulp of the longan Lour fruit showed diverse effective health biological functions, for instance, flourishing blood metabolism, calming and relaxing nerves, alleviating insomnia, restraining amnesia, enhancing longevity, relieving nerve pain, curing nerve swelling, and medicating palpitations [14]. Additionally, for a long time, the longan plant was used to treat fatigue diseases. The phytochemical constituents of the flowers and seeds of longan decrease the pain associated with urinary disorders. However, the flower, root, pulp, and pericarp have antioxidant, anti-glycation, anti-tyrosinase, antifungal, anti-microbial, and anti-cancerous activities. For these reasons, these parts are used in medication for diabetes, cancer, fungal, microbial infections, etc. [14,49]. In Bangladesh, the local "kaviraj" in Barisal use it for different diseases, such as gastrointestinal disorders, cuts and wounds, fever, snake bites, menstrual problems, chickenpox, bone fractures, cattle disorders, and so on; it is more prevalently used as the antidote for poison [47]. In Tabgail, longan is used locally to treat neurological disorders and reproductive health [52].

Nutrient Components and Phytochemicals Profiling of Dimocarpus longan 3.4.1. Nutrient Components of the Fruits
Carbohydrates (12-23%), potassium (196.5 mg/100 g), ascorbic acid (43.12-163.7 mg/100 g), and water (about 80%) are all contained in fresh longan pulp [8]. Despite not having the maximum polysaccharide content, the fruit pulp is the edible portion widely used in traditional medicine [53]. Fresh longan fruit is rich in nutritional components and free amino acids [54]. Dietary compositions and amino acid compositions are illustrated in Tables 1 and 2, respectively. Fresh longan fruit pulp contains potassium (266 mg/100 g), which maintains the proper functioning of nerves and muscles of humans [14]. Additional minerals, including iron (Fe), calcium (Ca), phosphorus (P), and magnesium (Mg), are abundant in longan fruit pulp. longan fruit pulp is rich in vitamins such as vit-C (ascorbic acid), riboflavin, thiamin, and niacin (Table 1). Furthermore, water, protein, ash, carbohydrate, and fiber are available in the Lour. fruit pulp. Fresh longan fruit pulp contains seven essential amino acids, and most importantly, few free amino acids, namely, glutamic acid (Glu), alanine (Ala), aspartic acid (Asp), valine (Val), and leucine (Leu) are found ( Table 2).

Pharmacological Activities of Dimocarpus longan
The pharmacological investigation of the D. longan Lour are as follows and the data are summarized in Table 4.

Antiproliferative, Antioxidant Activity and Anticancer Activity
The excessive, abnormal, and uncontrolled growth of the body's tissue cells are characteristics of cancer. Cancer cells (invasive) infiltrate and continue to expand the surrounding tissue (metastasis). Secondary metabolites are plant-derived compounds with bioactivity that can inhibit cancer cell proliferation [56]. The antiproliferative activity of D. longan leaf extracts against cell lines derived from cancer was studied in a controlled environment and in in vivo research models. The research study also established that longan leaf ethanol extract possessed significant antiproliferative activity against cancer-derived cell lines. Table 4 also shows the significant pharmacological activities of isolated compounds of longan. The highest antiproliferative activity was obtained by extracting WEHI-164 at 600 µg/mL and 57.45 percent by 500 µg/mL of ethanol at THP-1 at 44.93 percent [57].
Antioxidants are the chemical substances that can improve shelf-life by delaying the oxidation process when incorporated into cellular components, namely, DNA/RNA, protein, and lipid molecules, which are one of the main reasons for foodstuff degradation during production and storage [58]. Accordingly, bioactive compounds, particularly from plant sources, have become more critical in recent years [59]. Many plant-derived bioactive compounds, and crude vegetable and fruit extracts were known to positively affect the free radicals in biological systems as significant antioxidant compounds [60,61]. The pericarp of the longan fruit is densely packed with bioactive substances such as phenolic compounds, polyphenols, hydrolyzable tannins, and polysaccharides. Those compounds had considerable antioxidant activity in different models of antioxidants, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, radical scavenging activity of superoxide anions, total antioxidative capacity, and inhibitory lipid peroxidation activity [22]. Phenolic compounds of longan plant parts have long been thought to possess significant antioxidant and free radical scavenging properties, due to its ability to suppress the enzymes responsible for the production of reactive oxygen species (ROS) and to reduce rapidly oxidized ROS [62,63]. To further investigate the findings of various research, Fu et al. discovered that longan possessed a ferric reducing antioxidant power (FRAP) value of 8.61 ± 0.44 µmol Fe (II)/g and a total phenolic value of 5.88 ± 0.34 µmol Trolox/g. The study also revealed a strong interaction (R2 = 0.8416) among the FRAP value and total phenolic content [59,64]. Several crops of longan have been studied for their antioxidant potential, and the cellular antioxidant activity (CAA) scores ranged from 0.49 to 6.71 mol quercetin equivalents (QE)/100 g of fruit with an average value of 2.76 mol QE/100 g of fruit. According to CAA values, the antioxidant activity of longan fruit appears to be dominated by phenolics and flavonoids [11]. The FRAP value of longan plant seed was also greater compared to the longan peel and pulp [65], in which the pulp has the lowest FRAP value within the three components. In addition, 4-O-methyl gallic acid and (-)-epicatechin also have antioxidant capabilities and health benefits extracted from the pericarp [22].
It is now known that cancer is the number one health threat to the general population, and thus we need to prevent and treat it by using potential strategies [66]. It is increasingly a preventable disease because cancer develops progressively slowly and takes many years to become a life-threatening condition [67][68][69]. A pure polysaccharide (LPS1) derived from the pulp of the longan plant has a dose-dependent manner for the significant effect on hepatoma cells, most likely due to the immunomodulatory activities of (1-6)-α-D-glucan [29]. The research study by Iteku Bekomo Jeff and colleagues demonstrated that the anti-cancer activity of the glucans (1-3)-β-D-glucan and (1-6)-α-D-glucan were confirmed [30]. In the in vitro studies, a new water-soluble polysaccharide derived from the longan pulp (LP1) demonstrated a significant anti-tumor effect on the SKOV3 and HO8910 cancer cell lines, with the antiproliferative percentages of 40 percent at a concentration of 40 mg/L and 50 percent at a concentration of 320 mg/L, respectively, at different concentrations [12]. Four extracted longan polysaccharides (LP I-IV) and refined longan pulp polysaccharides inhibited the proliferation of A549, HeLa, and HepG2 cancer cell lines at different concentrations ranging from 5.6 to 16.8 percent, 8.3 to 23.2 percent, and 4.7 to 29.5 percent, respectively, and LP III inhibited A549 and HepG2 cells more strongly than refined or crude longan pulp polysaccharides [31]. The insights of the factors associated with polysaccharide anti-tumor function were in the following order: water solubility > chain conformation > average molar masses (Mw) [70]. According to cancer epidemiological studies, enhancing the consumption rate of phenolic contents is associated with a lower risk of cancer formation [71][72][73][74]. Three phenolic compounds exhibited significant anti-cancer activity in the HepG2, A549, and SGC 7901 cancer cell lines: gallic acid, corilagin, and ellagic acid [19]. Chih-Cheng   [32] noted that the extracted compounds of longan flower and seed possessed strong anti-cancer potential on several cancer cell lines through inhibiting the cancer modulatory pathways.

Anti-Inflammatory Properties
Inflammation has been defined as the tissue's localized protective response to injury or infection, manifested by pain, redness, and swelling. The inflammatory process involves several physiological systems with a central role in the immune system. Several molecules and signaling pathways are upregulated in damaged areas as a result of inflammation. The inducing features of nitric oxide synthase (iNOS) and cyclooxygenase-2 are these proinflammatory enzymes (COX-2). Increased levels of nitric oxide (NO) and prostaglandins (PGs) are caused by the genes iNOS and COX-2, respectively [75]. Most strong evidence for NO's role as a mediating role of the inflammatory response has come from studies on an animal rheumatoid model, human osteoarthritis, and rheumatoid arthritis, among other sources [76].
Additionally, to cope with the increase in oxidative stress and inflammation that occur during injury, tissues contain antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In recent times, it was demonstrated that dysfunctional cellular antioxidant mechanisms contribute to the development of a number of adverse and cancerous diseases in organisms [77]. There is evidence that the critical roles played by antioxidant enzymes in the inflammation pathway defend the organisms from oxidative stress [78]. The suppression of NO and tumor necrosis factor (TNF) as well as the enhancement of antioxidant enzyme activities, such as catalase, superoxide dismutase, and glutathione peroxidase, have shown that the water extract of longan pericarp (WLP) has anti-inflammatory properties [33].

Immunomodulatory Activities
Polysaccharides derived from a variety of natural sources have been shown to possess immunomodulating properties [14,79]. LPD2, an effective polysaccharide derived from longan pulp, demonstrated a significant effect on the upregulation of macrophages phagocytic effect as the multiplication of splenic lymphocytes through the toll-like receptor 2 (TLR2) and 4 (TLR4) facilitated myeloid differentiation factor 88/interleukin receptor-associated kinases (MDF88/ILRK) signaling pathway and the tumor necrosis factor receptorassociated factor 6 (TRAF6) signaling pathway [12,[80][81][82]. The major reason why LPD2 is the stronger immunomodulatory substance is higher molecular weight, acetyl groups, and (1-4)-β-Glc. LP1 and LP1-S were shown to significantly raise the pinocytic effect of murine macrophages and development of nitric oxide (NO), interleukin 6 (IL 6), interleukin (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in vitro, according to experimental research [83]. Cytokines released during the immune response by the helper T-lymphocyte play a significant role in controlling the existence of the reaction. For instance, type 1 helper T-cells (Th1 cells) release interferon (IFN-γ) and interleukin-2 (IL-2) to modulate cellmediated immunity [84]. IFN-is a multifunctional cytokine that has immunomodulatory effects on a variety of immune cells. IFN-has been shown in mammals as a marker of cellular immunity in infected organisms [85]. Consequently, the IFN-α detection can be made to preliminarily evaluate T cell activation's extent [86]. The water-soluble polysaccharide (LP1) extracted from Dimocarpus longan pulp has shown solid immunomodulatory activities. The research studies have significantly demonstrated that the LP1 have effectively regulated the expression of the cytokine interferon-γ (IFN-γ) and enhanced the activity of murine macrophages and the B-and T-lymphocyte production [12].

Prebiotic Activities
Prebiotics are the functional foodstuffs categorized as edible products that have to be measured by their health benefit by their intake in the bloodstream, and by the component's main activity [87]. The non-digestible carbon-hydrates, such as resistant starch, galactooligosaccharides (GOS), fructo-oligosaccharides (FOS), and various oligosaccharides that produce carbohydrates fermentable by advantageous colon microorganisms are prebiotics that are obtained from natural sources such as vegetables, rootstock, fruit, milk, or honey [88,89]. The research studies noted that the longan pulp polysaccharides showed intense prebiotic activity on several probiotic bacterial strains. The superfine grinding-assisted enzymatic treatments (LP-SE) of longan pulp polysaccharides exhibited the most important prebiotic activities with great potential in the use of functional food and medical industries [90]. The polysaccharides from the pulp of longan had more significant effects on Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus fermentum, and Leuconostoc mesenteroides than LP-H (longan pulp polysaccharide extracted using warm water) and LP-S (longan pulp polysaccharide extracted using superfine grinding) [90]. Longan cellulose with a degree of hydrolysis of 21% demonstrated a greater prebiotic significance and growth level of bacteria for Lactobacillus acidophilus and Bifidobacterium lactis [91].

Anti-Microbial Activities
Plant extracts and phytochemicals, both of which have been shown to have antimicrobial properties, can become very useful in therapeutic approaches [92]. Several studies in various countries have been carried out to demonstrate this efficiency [93]. Due to the production of compounds in the plant secondary metabolic pathways, several species of plants have been used for their anti-microbial properties. These products are characterized by essential ingredients, such as phenolic content found in essential oils known as tannin [94,95]. The anti-microbial properties of longan Lour seed extracts were examined using disc diffusion methods, and the minimum inhibitory concentration was determined. The DL-P01-SI01 (Dimocarpus longan: crude methanolic extract; fractions: DL-P01, aquation; ethyl acetate subfractions) fraction demonstrated the highest activity against Staphylococcus aureus and methicillin-resistant S. aureus at an MIC of 64 mg/mL, attributed to the phenolic compounds [24]. Apriyanto et al. (2015) [34] reported that the longan tree leaf extract possesses activity towards the hepatitis-C virus and minimizing of death rate. Anti-influenza activity has also been noted by the chemical components from the parasitic plant on Dimocarpus longan Lour [35].

Anti-Fungal Activities
Intermittent fungi cause severe disease and mortality in patients with weak immune conditions [96]. Candida can be found in the normal flora of the mouth, skin, intestines, and vaginal area. Candida albicans is one of the Candida species found in the oral cavity and is responsible for most oral candidal infections [97]. Cryptococcus neoformans is a yeastlike encapsulated fungus that causes central nervous system and pulmonary problems in immunocompromised people and is an opportunistic fungal infection in both plants and animals [98,99]. The results of many studies have shown that longan seeds have antifungal activity against opportunistic yeast (Candida species and Cryptococcus neoformans). Ellagic acid showed the most potent anti-fungal activity, followed by corilagin and gallic acid, respectively, from all the extracted longan compounds. Candida krusei and some Candida albicans clinical strains were more efficiently suppressed by ellagic acid than Candida parapsilosis and Candida neoformans [36]. The significant pharmacological activities of isolated compounds of longan are represented in Table 4.

Neuroprotective Activities
Human brain synaptic vesicles contain the neurotrophin, brain-derived neurotrophic factor (BDNF), composed and deposited in the synaptic lesions to respond to endogenous or exogenous transmissions. Integration with the trkB receptor or the p75NTR receptor reveals its characteristics by interacting with the tropomyosin-related tyrosine kinase receptor B (trkB) or the p75 neurotrophin binding site p75NTR [100,101]. BDNF, which assists in neuronal transmission and memory incorporation, is an important component in producing and maintaining long-term memory synaptic transmission [102,103]. Neurogenesis appears to occur repetitively all throughout adulthood in two areas of the adult brain, known as the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus (DG) of the brainstem [104][105][106].
Additional findings have shown that brain-derived neurotrophic factor (BDNF) is necessary to preserve neuronal cells throughout development and neurogenesis [107,108]. In general, it seems that BDNF cascades and neurogenesis are a memory development procedure. In recent years, a growing number of studies have focused on neuroprotective strategies involving dietary supplements for the therapeutic interventions of central nervous system neurodegenerative disorders [109][110][111]. In the mice research model, the extracted compounds from the longan fruit part have shown a strong neuroprotective effect through enhancing the survival of immature neurons [39]. The research study by Anya Maan-Yuh Lin and colleagues reported that the water extract of longan flower possessed a potent neuroprotective effect in the brain rat model developed with the MPP + -induced neurotoxicity [40].

Anti-Aging Activities
Ageing is characterized by progressive disintegration of cells, a significant risk factor for developing a wide variety of degenerative diseases, including cardiovascular disease, neurodegenerative disease [112], and even skin ageing [113]. Many other research studies also reported that the phytochemical component of longan leaves showed potential anti-ageing characteristics. The longan leaves hydroethanolic extract (HE) demonstrated radical activity in the experimentation of DPPH and hydrogen peroxide with IC 50 values of 30.03 ± 7.64 and 71.40 ± 15.30 µg/mL, respectively. Moreover, it showed inhibition of lipid peroxidation with IC 50 of 537.01 ± 42.32 µg/mL. The HE was found to inhibit hyaluronidase and collagenase with IC 50 of 234.80, 21.52 and 314.44 62.14 g/mL, respectively. The extract also showed inhibition of MMP-2 and MMP-9 that is more potent than gallic acid by zymography at 1.0 mg/mL [38].

Anti-Diabetic Effect and Anti-Hyper Glycemic Effects
Diabetes mellitus (DM) was one of the world's leading causes of death. This figure is expected to reach 438 million by 2030 when misdiagnosed cases of diabetes are also included [114]. Subsequent studies have shown that hyperlipidemia and oxidative stress each play an important role in developing diabetes, with each increasing the risk of abnormalities [115]. As a result, there are many oral hypoglycemic medication therapies for the management of diabetes, such as biguanides and sulfonylureas, but these medications can produce severe side effects [116]. The research study by Ya-Yuan Tang and colleagues reported that the polyphenols and alkaloids from extracted by-products of the longan fruits possessed a strong anti-diabetic effect in vitro [18]. The pericarp extract of the longan plant revealed the potent anti-diabetic with anti-hyperglycemic activity in the mouse model by enhancing the gene expression associated with the production of insulin [17]. Moreover, the seed extract also showed strong anti-diabetic and anti-hyperglycemic effect on both the in vitro and in vivo research models by inhibiting the glucosidase activity [41].

Anti-Tyrosinase Properties
Browning of crude fruits, vegetables and beverages is a serious problem in the food processing industry and one of the major causes of postharvest quality loss during collection and management [117,118]. Browning of fruits and vegetables due to enzymatic action is primarily due to the oxidation of endogenous phenolic compounds [119]. The phenolic oxidation is known to be caused by an enzyme that is known as tyrosinase (monophenol, o-diphenol: oxygen oxidoreductase; EC 1.14.18.1). It is widespread in microorganisms, animals, and plants and is also responsible not only for plant browning but also animal melanization [120].
It has been demonstrated that the longan pericarp extract has anti-tyrosinase activity. When looking at ultra-high-pressure-induced extraction of 500 MPa and traditional extractions, the longan pericarp extract from the ultra-high-pressure-induced extraction exhibited the greatest proportion of anti-tyrosinase property, 23.6 ± 1.2% at the concentration of 100 g/mL, when compared to traditional extraction [121]. The mechanism of action of some tyrosinase inhibitors is via hydrophilic groups that attach with the active site of an enzyme, causing steric hindrance or altered conformation [122]. According to the study by Rout and Banerjee, the ultrasonication of polysaccharides from longan fruit pericarp (PLFP) inhibited tyrosinase activity non-competitively [123,124]. A wide variety of tests conducted on fresh and processed longan seed extracts revealed tyrosinase inhibition, and the IC 50 values for fresh and processed extracts were 2.9 and 3.2 mg/mL, comparatively [23]. The polyphenols of longan have also been shown to have tyrosinase inhibitory activity. In their study, Guan et al. discovered that the inhibitory effect of longan polyphenol extract on tyrosinase activity was dose-dependent. The inhibitory impact also resulted in a high sample concentration rate. It is conceivable that ellagic acid, gallic acid, corilagin, and ethyl gallate are responsible for inhibitory activity. Such compound holds various hydroxyl groups that are structurally similar to the substrate and have the potential to attach to the copper ion active site of tyrosinase, removing active oxygen and inhibiting tyrosinase enzyme expression [14]. The results of inhibitory activity studies confirmed that longan polyphenols inhibited tyrosine diphenolase in a reversible and competitive manner. As a result, the combined effect of longan polyphenols and substances with enzymes does not create an irreversible change in the cognitive shape of the enzyme. It uses longan polyphenols as a highly competitive aid to copper ions that inhibits tyrosinase formulation in the catalyzed reaction, which ultimately reduces the level of tyrosinase in the reaction mixture. Kubo et al. also characterized the methodology by which quercetin inhibits tyrosinase activity; they discovered that quercetin inhibits tyrosinase activity compared to active tyrosinase centers [42].

Miscellaneous Activities
Obesity is regarded as serious health condition that leads to the manifestation of diverse health problems, including cardiovascular disease, diabetes mellitus, hypertension, fatty liver, some cancers, mental health problems, and so on, and thereby this is a lifethreatening problem [125], as these conditions increase the lipid levels of our bodies. Here, the longan flower water extract directly ameliorates the hyperlipidemic effects and obesity with such effective activity showed by the polyphenol compounds. The following mechanisms act as control of the expression level of hepatic PPAR-alpha gene, regulation of SREBP-1c with FAS gene expression, reducing the exogenous lipid absorption, and the large amount of the fecal TG (triglyceride) output. Additionally, the total biological process occurred within the in vitro rat model in a dose-dependent manner [43,44].
A study by Zhu et al., 2016 [13], demonstrated that the polysaccharides of D. longan pulp could significantly promote the upregulation of sox9, aggrecan, and collagen II gene expression, consequently, synthesis of the CAM (cartilage extracellular matrix) protein as well as chondrocyte act as an excellent activity towards osteoporosis; the experiment was conducted within an in vitro model animal. On the other hand, D. longan fruit extract directly involves the activation of Erk-1/2 (extracellular signal regulated kinase-1/2) enzyme-dependent-RUNX-2 (Runt related transcription factor-2) factors via following the phosphorylation mechanism along with initiating the differentiation of osteoblasts. Longan fruit extract also represses the mRNA expression of osteoclast and thereby inhibits the differentiation of osteoclast, mediates the osteoporosis disease severity, and decreases the TRAP (tartrate resistant acid phosphatase) protein-mediated multinucleated cells in the RAW264.7 cells [14]. Additionally, NF-κB (nuclear factor-kappa B) pathway downregulation, NFATc1 (nuclear factor of activated T-cells c1) suppression through the longan Lour fruit extract efficiently involves the suppression of osteoclast differentiation in vitro. Additionally, the administration of Lour fruit extract in vivo experiment model ovariectomized rats and zebrafish enhanced their mineral contents in bone, minimizing bone disorder risk [126,127]. Longan Lour flower H 2 O extract attenuates the serological TG (triglyceride), disaggregates the lipid moiety, and downregulates the MMP-2,9 (matrix metalloproteinases-2,9) gene expressions, thereby protecting the hepatic cells; in vitro hypercaloric-dietary rat model study [28].

Concluding Remarks
Nowadays, natural food products are given more attention by people to combat diseases, including cardiovascular diseases, immune dysfunctions, and cancer insurgencies. Additionally, consumers are turning to compounds derived from medicinal plants to treat a wide range of conditions, including malignancy, due to the lower risk of complications and lower cost of these biomolecules. It was recently found that researchers from pharmaceutical sectors and medication are searching for natural compounds as medicinal agents since synthetic compounds show substantial side effects to the patients' bodies. For this reason, this review was conducted to explore natural phytochemicals that offer therapeutic activities; as a model plant, Dimocarpus longan Lour was reviewed, and it significantly exhibited a diverse group of chemical compounds. As a source of flavonoid and phenolic components, this plant displayed different biological activities, and more interestingly, it showed strong anti-cancer and anti-diabetic activities.
Consequently, this review article has demonstrated that the compounds derived from Dimocarpus longan Lour will be used as a complementary and alternative medicine to treat many different types of diseases. They can also serve as possible sources of phytotherapeutic lead molecules. However, according to previously published research, the pharmacokinetic evidence for this promising, highly nutritious medicinal plant and its derivative products is insufficient in this case. Therefore, more research on these natural compounds is highly required, especially on their toxicogenetical profiles. Therefore, more research is needed to discover the specific disease controlling and toxicological mechanisms and their pharmacokinetics properties.