A Comprehensive Review on the Chemical Composition and Pharmacological Activities of Acacia catechu (L.f.) Willd

With the emergence of epidemics, pandemics, and infectious diseases, several research activities have been carried out on natural products to tackle them. As there are structural diversities in natural products, researchers are focused on exploring them for treatment and/or management of various infections and/or diseases. Acacia catechu (L.f.) Willd. belonging to the order Fabales and family Fabaceae shows a wide range of pharmacological functions in the management of diseases in humankind. *is review was carried out to gather and provide information about the chemical constituents and pharmacological activities of A. catechu through the literature survey of scientific articles. On preliminary assessments, A. catechu is demonstrated as a significant wellspring of bioactive compounds with a wide range of biological and pharmaceutical applications such as antidiabetic, antioxidant, antimicrobial, anticancer, antidiarrheal, anti-inflammatory, antiviral, hepatoprotective, immunomodulatory, and so on. Although the metabolites from the plant are reported with diverse pharmacological applications, there is little information in regards to toxicity and clinical trials on bioactive compounds of this plant. Further research on diverse bioactive compounds from the plant is required to develop them as a successful potent drug.


Introduction
With the beginning of civilization, humans have been messed with various infectious diseases and many lives have battled in adapting to them. Various preventive and/or treatment approaches have been established to counter them. Among them, natural products are a rich source or tool of research for the management of diseases for the welfare of humankind [1][2][3]. Isolation and identification of bioactive compounds or drugs from natural products' pool have a long history [4], and research on them has acquired tremendous profound due to their bioactive functions against different infections, diverse nature and structural complexity, cost-effectiveness, and least side effects [5,6]. More than 50% of all drugs witnessed in modern medicines are through natural products and their derivatives [7]. In other words, approximately 35% of the global market of medicines have been run or originated through natural products [8]. With the growing research on medicinal plants, A. catechu is also one of the important bioactive plants.
is study explores on chemical constituents and pharmacological functions of A. catechu through the literature-based analysis.
e scientific information about A. catechu was gathered from articles by searching them in Google Scholar, PubMed, Elsevier, ScienceDirect, Scopus, Springer, Wiley online library, and Web of Science.

Chemical Composition and Pharmacological Applications
A. catechu contains phytochemicals with diverse pharmaceutical and biological activities ( Figure 1) [23]. Several factors such as climatic conditions, harvesting time, storage conditions, development stages, variability, and genetic factors are responsible for diversities in their secondary metabolites [24]. On phytochemicals screening of methanol extract of A. catechu heartwood; tannins, terpenoids, triterpenoids, alkaloids, ascorbic acid, and carbohydrates were tested positive [25], while leaf extract showed the presence of resins and saponins additionally [10]. In another study, methanol extract of plant bark showed the presence of alkaloids, carbohydrates, flavonoids, tannins, and steroids [26].

Antiviral Activities.
On cell-free virus-based assay using reporter-gene-based TZM-bl cells and HIV-1 NL4.3 (X-4 tropic), the aqueous, 50% ethanolic, and butanol extracts of A. catechu showed anti-HIV-1 activities with IC 50 values of 1.8 ± 0.18, 3.6 ± 0.31, and 1.7 ± 0.12 μg/mL, respectively, probably by inhibiting the activities of the viral protease and Tat [50]. e butanol fraction shows anti-HIV protease activity with an IC 50 of 12.9 μg/mL. Antiviral activity is via blockage of RNA synthesis and inhibition of assembling and maturation of virus particles in infected cells [50].

Antidiarrheal Activities.
In an in vitro study in Guinea Pig, A. catechu extract showed beneficial activities towards diarrhea patients via spasmolytic and antispastic activities through interaction with calcium channels and muscarinic receptors [37]. Extract of plant showed a noncompetitive reversible antagonism to carbachol in proximal colon (IC 50 � 0.74 mg/mL) and ileum segments (IC 50 � 0.98 mg/mL) [37]. In another study, bark extract of plant showed a significant (P < 0.05) concentration-dependent antidiarrheal activity through castor oil-induced diarrhea experiment [26]. During the experiment, extracts (200 mg/kg and 250 mg/kg) showed a reduction of diarrhea by 20 and 40% [26].

Anti-Inflammatory Activities.
Nitric oxide is useful for several physiological functions, but overproduction results in inflammatory diseases [80,81]. A. catechu controls the production of nitric oxide by peritoneal macrophages in a dose-dependent manner [17]. A. catechu increases the secretion of IL-10 (plays a role in immunoregulation and inflammation) and inhibits the production of TNF-α (mediator of inflammatory response) secreted by monocytes and macrophages [17].

Hepatoprotective Activities.
A study showed the inhibiting ability of ethyl acetate extract of A. catechu (250 mg/kg) towards tetrachloride-induced liver toxicity in albino rats through biochemical (estimation of serum transaminase, serum alkaline phosphatase, and serum bilirubin) and histopathological values [86]. A. catechu herbal extracts were shown as hepatoprotective with the IC 50 of 114.8 μg/mL on HepG2 cells toxified with tert-butyl hydroperoxide (t-BH) [27]. e antioxidant potential of this plant attributed hepatoprotective activity via diminishing lipid peroxidation and cellular damage [27]. Similarly, from an in vivo model, ethyl acetate extract of the plant showed significant hepatoprotective ability [42]. Nonetheless, the seed and bark extract of A. catechu showed hepatoprotective activity via decreasing lipid peroxidation, reducing the activity of liver enzymes (alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase), and increasing the antioxidant activity through an increase in activities of glutathione and superoxide dismutase in Wistar rat model experiments [87].
3.9. Immunomodulatory Activities. Upon treatment of extracts of A. catechu, the number of antibody-producing cells in the spleen increased with 535.67 ± 1.69 and 370.50 ± 1.33 plaque-forming cells (PFC)/10 6 spleen cells for ethanol and aqueous extracts at 200 mg/kg [17]. e butanol fraction of plant extract rich in catechins was shown with beneficial abilities on the immune system [28]. Another study showed the increment of serum immunoglobulin levels and hemagglutination titer values, and the decrease in the mortality rate on feeding the plant extracts to mice results in the immunomodulatory activity [88].

Additional Applications
3.10.1. Antiulcer. Aqueous extract of A. catechu showed a significant reduction in total acidity, number of ulcers, volume of gastric juices, and the activity probably due to action on the membrane of microorganism, by the accumulation of mucus, by inhibiting H + K(+)-ATPase, and by decreasing mucosal hemorrhage and erosion [45]. Also, tablets prepared from A. catechu extracts were effective in the prevention and/or treatment of mouth ulcers [89].

Antinociceptive.
A. catechu exhibited the dose-dependent antinociceptive activity probably due to blockage of prostaglandins synthesis by extracts which might be effected through the inhibition of activities of cyclooxygenase and lipoxygenase [19].

Antipyretic.
In albino rats, ethyl acetate extract of A. catechu was shown with antipyretic activity (P < 0.01) at a concentration of 250 and 500 mg/kg [42]. Similarly, Dubey et al. showed the antipyretic activity of the hydroalcoholic leaf extract of the plant [90].

Neurodegenerative Disorders.
e methanol extract of A. catechu showed potential in the management of neurodegenerative diseases (Alzheimer's disease) via the anticholinesterase effect and significant antioxidant effect [91]. Also, the water extract of the plant stem shows acetylcholinesterase (AChE) inhibitory activity with an IC 50 of 0.95 mg/mL [92].

Wound Healing.
e plant extract showed wound healing activities on the excisional wound model with a significant increase in collagen and granulation tissue on day 21 in guinea pigs [93]. e development of bioactive compounds with pharmacological functions as a drug depends upon their pharmacological parameters such as absorption, distribution, metabolism, excretion, and toxicity properties. A study showed the ethanolic extract of A. catechu seed with low mammalian toxicity through hematological and biochemical parameters analysis [94]. Additionally, Lakshmi et al. showed that ethanolic seed extract of the plant plant with marked cytotoxic effect on brine shrimps assays [95]. Further in vivo and/or clinical assays are required to explore them as a potent drug.

Conclusions
A. catechu being a rich source of bioactive secondary metabolites, especially polyphenols, could be a promising material for research in drug discovery against different diseases. e plant was shown with wide pharmacological functions such as antioxidants, antidiabetic, antimicrobial, anti-inflammatory, antiviral, and anticancer abilities. Further research is required to evaluate the plant extracts and their active bioactive compounds as drugs or food compliments.

Conflicts of Interest
e authors declare no potential conflicts of interest.
Journal of Chemistry 7