Major Bioactive Alkaloids and Biological Activities of Tabernaemontana Species (Apocynaceae)

Several species belonging to the genus Tabernaemontana have been well researched and utilized for their wide-ranging biological activities. A few of the most prominent species include Tabernaemontana divaricata, Tabernaemontana catharinensis, Tabernaemontana crassa, and Tabernaemontana elegans. These species and many others within the genus often display pharmacological importance, which is habitually related to their chemical constituents. The secondary metabolites within the genus have demonstrated huge medicinal potential for the treatment of infections, pain, injuries, and various diseases. Regardless of the indispensable reports and properties displayed by Tabernaemontana spp., there remains a wide variety of plants that are yet to be considered or examined. Thus, an additional inclusive study on species within this genus is essential. The current review aimed to extensively analyze, collate, and describe an updated report of the current literature related to the major alkaloidal components and biological activities of species within the genus Tabernaemontana.


Introduction
The genus Tabernaemontana belonging to the family Apocynaceae was named by a German physician and botanist, J. Th. Muller [1]. At present, approximately 100 species belonging to this genus have been distributed in tropical and subtropical regions around the world, including Africa, Asia, Oceania, and the Americas [2]. Tabernaemontana species consists of flowering shrubs and small-medium-sized trees, which habitually grow in the savannahs, rocky outcrops, and forest understories [3]. Characteristic features of the genus include tubular white flowers, follicular fruit with seeds embedded within a yellow to reddish aril, and a milky or watery latex exudate, which is often found in wounded species [4]. Due to the latex content, plants within this genus are usually called "milkweed" and are often used for their biological activities [2,5,6]. Plants within the genus Tabernaemontana obtain a profusely high alkaloid content, usually displaying pharmacological activity [2]. Furthermore, monoterpene indole and bisindole alkaloids are the major classes of alkaloids within the genus, and other compounds include terpenes, lactones, steroids, phenolics, and flavonoids [1]. Over 67 species have been investigated for indole alkaloids, of which 470 isolations of approximately 240 structurally different bases have been detected [2,3,7].
A few of the most intensively studied Tabernaemontana species include T. divaricata, also known as "Crape Jasmine", which occurs in the tropical regions of southern China, India, and Thailand [8]. Crape Jasmine is intensively utilized as an aphrodisiac, tonic, and a purgative [8]. According to Van Beek et al. [1], in western India, latex is used for
The findings of Nicola et al. [9] provide scientific support to the frequently used traditional medicinal plant T. catharinensis. The outcomes of the study revealed the presence of major alkaloids, such as 16-epi-affinine, coronaridine-hydroxyindolenine, voachalotine, voacristine-hydroxyindolenine, 12-methoxy-n-methyl-voachalotine, and a derivative of voacristine or voacangine (Table 1). It was suggested by Nicola et al. [9] that these chemical constituents exhibited anticholinesterase activity and can be recommended for the future treatment of neurodegenerative disease. According to Mairura [45], a substantial amount of indole alkaloids have been identified and isolated from the stem bark, rootbark, and seeds of T. crassa. Major alkaloids include those of the ibogan class, such as coronaridine, monoand di-methoxy derivatives of isovoacangine, conopharyngine, and the aspidospermatanclass apparicine (Table 1). Mairura [45] explained that the plant is highly toxic, as crude ethanolic extracts were found to be lethal to test subjects. Conversely, the study of Kuete et al. [73] investigated the toxicity of hydro-ethanol stem-bark extracts and the results showed no toxicological activity, thus suggesting a novel source of naturally produced drugs. Ingkaninan et al. [53] investigated the phytochemical properties of the flowers, leaves, stems, and root extracts of T. divaricata. Additionally, four isolated compounds, namely 19,20-dihydrotabernamine, 19,20-dihydro-ervahanine A, conodurine, and tabernaelegantine A, were screened for biological activity. The findings revealed that the extracts and respective compounds displayed high antiacetylcholinesterase activity. Furthermore, studies have shown that isolated compounds from T. divaricata, such as conophylline, were effective against in several cell lines [74]. Previous phytochemical research has shown T. elegans to contain several monoterpenoid indole alkaloids of which 24 were previously isolated [56]. The major indole alkaloidal components extracted from the whole plant and root bark of T. elegans were vobasine, dregamine, and tabernaemontaninol [6,16,55]. A recent study by Pallant et al. [20] reported the isolation and identification of alkaloids in the root extract of T. elegans. Major components observed were dregamine and voacangine, which exhibited significant antibacterial activity against Gram-positive bacteria and Mycobacterium species.
Despite the variety of biologically active compounds displayed in the above-mentioned species and Table 1, several other Tabernaemontana species, such as T. ventricosa, lack an in-depth chemical and pharmacological investigation. A few studies have observed the bioactivity of T. ventricosa [1,75]. Van Beek et al. [1] reported that the alkaloid akuammicine, belonging to the strychnan class, exhibited opioid activity in opiate receptor studies. The same group investigated the antibacterial, antifungal, and antimalarial activities of T. ventricosa extracts; however, no activity was observed in vitro. Mehrbod et al. [75] investigated the effect of T. ventricosa plant extracts on the influenza A virus. This investigation supported the study of Van Beek et al. [1], as the results concluded that the leaf extracts of T. ventricosa were ineffective against the influenza A virus. Due to the traditional uses of T. ventricosa being very similar to those of other well-known studied species, little to no studies have been conducted on T. ventricosa, thus it is necessary to evaluate the complete medicinal potential of this species and other Tabernaemontana species to determine its probable pharmacological activities. Considering the several uses of Tabernaemontana species in traditional medicine, many of their proposed biological activities have been confirmed, others invalidated, while countless species remain undefined [2]. Additionally, the improvements in science and medicine have allowed the discovery of new properties of extracts, fractionations, and the identification and isolation of novel compounds [2].

Antioxidant Activity
Antioxidants are identified as molecules or compounds that regulate the process of autoxidation either by intersecting the movement of free radicals or directly constraining their formation [76,77]. Medicinal plants are often recognized for their rich source of antioxidants, which include phenolic acids, phenolic diterpenes, flavonoids, volatile oils, carotenoids, and anthocyanidins [77]. These compounds target free radicals by quenching oxygen molecules, breaking antioxidant chains, donating hydrogen molecules, or acting as reducing agents [76,78]. Therefore, antioxidants are suggested to decrease oxidative stress, improve immune function, and increase healthy longevity [76][77][78]. Several factors can alter the antioxidant capacity of a certain species; these include the rate of reaction between the samples and the reactive species and the concentration ratio between the antioxidant and the target [2]. There are multiple methods used to determine the antioxidant activity of plant species; however, various methods may result in variation of the results [79]. Many species within the Tabernaemontana genus have been investigated for their antioxidant activity using different techniques, which include the inhibition and scavenging activity of reactive oxygen species and reactive nitrogen species, reducing capacity, and metal-chelating capacity [2]. The most frequently studied species within the genus is T. catharinensis [9]. Table 2 summarizes the antioxidant properties of Tabernaemontana species. Boligon et al. [80] investigated the crude leaf extracts and fractions of T. catharinensis by using the thiobarbituric acid reactive substances technique. Ethyl acetate and n-butanol fractions, yielding a half-maximal inhibitory concentration (IC 50 ) of 6.71 ± 0.19 µg/mL and 26.15 ± 0.08 µg/mL, respectively, displayed optimal results. Furthermore, the same study also assessed the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) inhibition of T. catharinensis extracts, which exhibited good results, with an IC 50 value of 4.64 ± 1.25 to 27.78 ± 0.93 mg/mL [80]. Additionally, Nicola et al. [9] examined the antioxidant activity of the alkaloidal fraction in the branch and leaf ethanolic extracts of T. catharinensis. The findings of the study revealed significant antioxidant activity from the alkaloidal fraction, with an IC 50 of 37.18 µg/mL [9].

Anti-Inflammatory Activity
Inflammation is defined as a compound biological process that involves an adamant response of an organism to injury or damage of tissue [109]. The development of inflammation is often induced by microbial infection, chemical injury, cell injury, and death [110]. The consequences of these inducers are primarily indicated by pain, redness, heat, and swelling, which arise due to the deviations in blood flow, capillary permeability, and afferent nerve fibers [111,112]. Subsequently, these changes imitate the restoration of inflamed tissue and constrain additional damage to the organism [109]. Based on the characteristics of inflammation, this composite process is divided into two major types known as acute and chronic inflammation [72,109,113]. Acute inflammation occurs almost instantly, or a few hours following injury, and usually displays symptoms of redness, heat, and edema [72]. Whereas, chronic inflammation occurs over an extended interval and is histologically characterized by the occurrence of lymphocytes and macrophages, which subsequently results in the development of fibrosis and necrosis tissue [114]. The standardized protocol for the evaluation of anti-inflammatory activity comprises ex vivo and in vivo experiments [2]. Many Tabernaemontana species have been assessed for anti-inflammatory activity. Table 3 summarizes those anti-inflammatory properties of Tabernaemontana species. Jolly et al. [93], investigated the anti-inflammatory activity of ethanolic flower extract obtained from T. divaricata. Mice models were subjected to acute carrageenan and chronic formalin [93]. The results showed significant anti-inflammatory activity in both models at a dose of 100 mg kg −1 , in comparison to the standard reference drug diclofenac (25 mg kg −1 ) [38]. Furthermore, Jain et al. [115] examined the in vivo anti-inflammatory activity of T. divaricata leaves. In this study, hexane fractionations containing a profuse source of flavonoids were tested on male albino mice [115]. The results revealed extensive anti-inflammatory activity, which displayed enhanced results in comparison to the positive drug indomethacin [115].

Antimicrobial Activity
Antimicrobials are defined as complex compounds that constrain the development of microorganisms at diminutive concentrations [128]. These compounds are often described as secondary metabolites and are regularly produced and extracted from medicinal plants or microorganisms [129]. The efficiency of antimicrobial activity is dependent upon several factors, such as various microbial strains, technique (in vivo or in vitro assay), and type of sample [2]. Studies have reported the evaluation of Tabernaemontana extracts as natural antibiotics [3]. Monoterpenoid indole alkaloids, such as voacamine type and 3-hydroxyiboga, are biologically active compounds and are reportedly used as antimicrobial agents, inhibiting the growth of bacteria, fungi, and parasites [3]. Tables 4-7 summarize the antifungal, antiviral, antibacterial, and antiamoebic properties of Tabernaemontana species.      [132] investigated the dichloromethane and n-butanol fractions of ethanolic leaf extracts from T. catharinensis. The dichloromethane fraction showed significant activity against the fungal strains C. albicans, C. glabrata, C. neoformans, S. cerevisiae, A. flavus, and A. fumigatus, with MIC ranging from 31.25 to 1000 mg/mL [132].

Antiviral Activity
Boligon et al. [132] evaluated the dichloromethane, ethyl acetate, and n-butanol fractions from the ethanolic extracts of T. catharinensis. The extracts and fractions displayed substantial antiviral activity on herpes simplex virus type 1 (HSV-1) in contrast to acyclovir (IC 50 1.5 mg/mL) [132]. Furthermore, significant antiviral activity was observed from the dichloromethane and ethyl acetate fractions. The dichloromethane and ethyl acetate fractions of the bark-stem fractions showed IC 50 values of 2.62 and 2.88 µg/mL, respectively, whereas the fractions of the leaves showed IC 50 values of 0.6 and 2.21 µg/mL, respectively [132]. It is suggested that biologically active compounds, such as steroids, terpenoids, and phenolics, found in the dichloromethane, ethyl acetate, and n-butanol fractions are accountable for the antiviral activity [2,132].

Antibacterial Activity
Over the past 50 years, extensive research has been conducted about the advancements in antibacterial medicines [175]. Moreover, due to the reoccurrence of multidrug-resistant bacteria, there is an excessive necessity for the development of novel and innovative antibacterial agents against those displaying multidrug resistance [175,176]. Approximately 25% of modern medication has been established on the core basis of plant-related compounds [177]. Thus, the active screening of medicinal plants is imperative for the discovery of new antibacterial compounds [178]. The indole alkaloids of Tabernaemontana exhibit a wide range of pharmacological activities, including antibacterial activity against Grampositive and Gram-negative bacteria [133]. Gindri et al. [150] investigated the antibacterial activity of ethanolic extract and its fractions from the leaves of T. catharinensis. The extracts and fractions were tested against multiple bacterial strains, such as S. aureus, Aeromonas sp., Micrococcus sp., P. mirabilis, E. coli, K. pneumoniae, E. faecalis, and P. aeruginosa, which were comparable against the antibiotics ampicillin (MIC = 8.0 mg/mL), cefoperazone (MIC = 16.0 mg/mL), and imipenem (MIC = 0.06 mg/mL). The findings showed positive results against Micrococcus sp., P. mirabilis, and P. aeruginosa (MIC values of 31.3, 62.5, and 62.5 mg/mL, respectively) [150].

Antiamoebic Activity
Parasitic infections are regarded as one of the leading contributors to human health problems and are often distributed via contaminated food and water sources [179]. Amoebiasis is a lethal disease that arises from the ingestion of pathogenic microorganisms and occurs predominantly in tropical areas, including China, Mexico, the Eastern portion of South America, South-East and West Africa, Asia, and the Indian subcontinent [180,181]. The protozoan parasite E. histolytica is dominant in these regions and affects approximately 12% of the world's population, whilst being responsible for copious mortality rates, ranging from 40,000 to 110,000 per year [180,182]. Since there is no vaccine against E. histolytica, metronidazole (MNZ) is regularly used to treat infection against amoebiasis; however, there are serious consequences of the drug, such as amoebic resistance and several side effects, including impaired physical and mental development [183]. Due to the severe side effects of MNZ, many infected people have opted for a more natural approach using traditional medicine [180]. Several Tabernaemontana species are often used in various parts of the world for their antimicrobial, antiparasitic, and antiamoebic action. Van Beek et al. [1] investigated a variety of Tabernaemontana species to establish their antiamoebic activity. In the study, approximately 15 Tabernaemontana species were tested against the protozoan E. histolytica. The study exhibited adequate results, as four extracts from three species showed promising activity below 0.5 mg/mL against the parasite protozoan E. histolytica [1]. Additionally, Uwumarongie et al. [141] evaluated the antiamoebic activity of T. pachysiphon root and stem bark extracts. The findings of their study showed relatively high antiamoebic activity against E. histolytica [141].

Anticancer and Cytotoxicity
The irrepressible division of cells habitually leads to the formation of cell masses, which are frequently termed as 'growths' or 'tumors' [184]. These masses are classified as malignant (cancerous) or benign (noncancerous) and are often influenced by several characteristics, such as an irregular diet, genetic factors, and ecological aspects [185,186]. These negative influences give rise to an amplified rate of cancer, since approximately 18.1 million people are expected to be diagnosed with cancer [187][188][189]. However, with the consistent applications of effective cancer treatments, such as radiotherapy, surgery, immunotherapy, and chemotherapy, these values may subside [190,191]. However, among these treatments, chemotherapy remains challenging due to the occurrence of multidrug resistance (MDR), which is defined as the resistance of tumors to chemotherapeutic agents [192]. Considering the above, the constant discovery of anticancer agents using medicinal plants has displayed minimal side effects and act as modulators of MDR. Thus, recently, several medicinal plants, especially within the genus Tabernaemontana, have been screened to evaluate their potential effect on the growth and development of cancerous cells [2].
The study conducted by Pereira et al.

Acetylcholinesterase Activity
Alzheimer's disease (AD) is defined as an advanced chronic and aggressive neurodegenerative disease, which is habitually accompanied by the severe disturbance of multiple cortical functions, including memory impairment, judgment, orientation, understanding, language learning capacity, and personality changes [235][236][237]. Clinically, this cognitive disorder is often characterized by the occurrence of several amyloidal beta-peptide plaques, neurofibrillary tangles, atrophy of basal forebrain cholinergic neurons, oxidative stress, and reduced neurotransmitter levels [9,238,239]. According to Adewusi and Steenkamp [240], AD is amongst the leading disorders worldwide as it is liable for approximately 50-60% of dementia in elders. Moreover, a dramatic incline, possibly affecting 7-10% of individuals over 65 and 40% of persons over 80 years, is anticipated within the next 50 years, without the intervention of rehabilitation [235,240,241]. Popular methods for the treatment of AD are often based on the cholinergic hypothesis, which suggests that the impairment of memory is directly related to a reduction in the function of cholinergic in the brain [241]. Thus, several approaches regarding the enhancement of acetylcholine levels using acetylcholinesterase (AChE) inhibitors are frequently investigated [239,241,242]. Currently, approved AChE inhibitors include tacrine, donepezil, rivastigmine, and galanthamine [238,241,242]. However, despite the beneficial effects on cognitive functioning, these inhibitors have displayed undesirable side effects, such as gastrointestinal issues, nausea, vomiting, and reduced bioavailability [243,244]. Considering the latter, the discovery of alternative natural AChE inhibitors displaying minimal side effects is essential [238,239,244]. Therapeutic plants have been investigated for their complex compounds that contain natural and innovative AChE inhibitors [241,242]. Several Tabernaemontana species have been recognized and investigated for their monoterpene indole alkaloids, which have demonstrated AChE inhibitory activity [245]. Ingkaninan et al. [241] investigated the AChE inhibitory activity of methanolic extracts of T. divaricata. In the study, extracts (0.1 mg/mL) were tested in vivo using rats as test models [241]. The results were promising as approximately 90% of AChE activity was observed. Furthermore, most recently, Athipornchai et al. [245] investigated the AChE inhibitory activity of the methanol, n-hexane, and ethyl acetate extracts of T. pandacaqui flowers. The results revealed that the ethyl acetate extract displayed the strongest AChE inhibitory activity, with inhibition of 35.4% at 5 mg/mL [245]. Considering the latter, prior and recent studies have shown the potential of plant AChE inhibitors, which should be further investigated. Table 9 summarizes the acetylcholinesterase activities of Tabernaemontana species.

Other Activities
Khan [98] investigated the gastrointestinal effects of the methanol extract from T. divaricata flowers. In the study, a rat pyloric ligation-induced gastric ulceration model was used to evaluate the potential effects, along with the standard drug omeprazole (8.0 mg/kg) [98]. It was revealed that the extract reduced the amount of gastric juice, free and total acidities, ulcer index, and pH of gastric acid produced [98]. The standard drug, omeprazole showed a percentage protection of 89.8%, and the extract 79.5% [98]. In another report, Khan et al. [250] further examined the methanol extract from the flowers of T. divaricata, using a range of concentrations (125.0, 250.0, and 500.0 mg/kg, p.o). Some inducers, such as aspirin and ethanol, were tested against gastric ulcers [209]. The standard positive control was misoprostol [250]. Several parameters, such as catalase, superoxide dismutase, mucin, and total protein, were measured and displayed a reduced index when treated with extracts. It has been suggested that the gastrointestinal effects of the extracts occur through an antioxidant pathway [250].
The antidiabetic activity of T. divaricata methanol extract was examined on alloxaninduced diabetic rats [251]. The results displayed substantial antidiabetic activity, with an additional reduction in the effect of oxidative damage observed in rats [251]. The extracts exhibited a similar mechanism in relation to the positive control, glibenclamide. The study of Kanthlal et al. [251] recommends that the methanol extract may alert the insulin receptors, therefore triggering a stimulation or production of beta-stem cells in the pancreas of the test subjects. The compound conophylline, which is often isolated from serval Tabernaemontana species, displayed antidiabetic activity [252]. Furthermore, conophylline was efficient in inducing the activity of activin A in AR42J cells, which in turn stimulated modification in endocrine cells [252]. The same compound was tested against diabetic rats [253]. In the study, increased plasma levels in normal and streptozotocin-induced diabetic rats were observed along with a significant decrease in blood glucose levels, indicative of antidiabetic activity [253]. In rat pancreatic acinar carcinoma cells and cultured rat pancreatic tissues, the compound conophylline was found to rapidly produce beta-cell differentiation, thus inducing differentiation into insulin-producing cells [74,253].
Tabernaemontana catharinensis is often used for its antivenom properties [2]. Almeida et al. [202] examined the antivenom effects. The alkaloidal aqueous fractionation from the root bark of T. catharinensis was tested in vivo using Crotalus durissus terrificus [202]. It was observed that the extracts were able to extensively defuse the poisonous action of the venom [202]. Núñez et al. [254], investigated the antivenom activity of T. elegans. The study observed potential inhibition against Crotalus durissus cumanensis venom [254]. The antivenom potential of T. alternifolia root extract was tested in vitro and in vivo against Echis carinatus venom [255]. A range of pharmacological assays, including lethal toxicity determination, hemorrhagic, and neutralization studies, were carried out using chick embryo models [255]. The extracts showed promising results, since fibrinogen degradation, hemorrhage, and the venom-induced edema were significantly reduced in the models [255]. Recently, Vineetha and coauthors [116] investigated the in vitro and in vivo inhibitory effects of T. alternifolia methanolic root extract against Naja naja venom. Similarly, in their previous study, the fibrinogenolytic, direct, and indirect hemolytic activities for the neutralization of the venom were observed [116,255]. The results of the study yet again showed great potential, since fibrinogen and hemolytic were neutralized effectively, and the edema ratio was significantly reduced [116,255]. The latex of several Tabernaemontana species is habitually utilized for its wound-healing effects [3]. Subsequently, T. catharinensis is known for its many medicinal uses, including wound-healing effects [2].

Silver Nanoparticles (AgNps)
Recent trends in science have promoted the synthesis of AgNps in the field of nanotechnology [256]. Nanoparticles are extremely small materials that exhibit nanoscale dimensions ranging from 1-100 nm [257]. Due to their nanoscale size, these particles display a large surface area to volume ratio [258]. The properties of AgNps, such as their size, shape, and morphology, have enhanced their activity and thus are used in an extensive range of applications, such as health, medicine, food, textiles, and agricultural sectors [257]. Many metals have been evaluated for the synthesis of nanoparticles, such as gold (Au), copper (Cu), and alloy of silver (Ag + ); however, comparable to these metals, reports have shown that Ag + is not considered a hazardous substance [259]. Gorchev and Ozolins [260] reported that minor amounts of Ag + were absorbed in laboratory test subjects ranging between 0% and 10%. The two main methods used to obtain nanoparticles comprise of a "top-down" approach, which can be described as the process whereby nanoparticles are reduced in size until they reach a suitable material; conversely, the "bottom-down" approach involves the development of nanoparticles from an elemental entity, such as atoms and molecules [261]. The top-down method consists of chemical and physical techniques that are often energy consuming and produce imperfect nanoparticles [262]. Moreover, the bottom-down technique includes biological methods, which regularly produces colloidal dispersions of homogenous particles with fewer defects [263]. Current research has shown that the biological synthesis (i.e., the use of living organisms) of AgNps has driven investigations towards a "greener synthesis" approach, which is simple, cost-effective, environmentally friendly, and easily upscaled for large-scale synthesis [256,264]. According to Chouhan [258], the method of biological synthesis using a greener approach is relatively simple, as it requires less time and energy comparable to physical and chemical methods. This approach involves incubating crude aqueous extracts obtained from various plants or plant organs with an aqueous solution comprised of a metal salt, such as silver nitrate (AgNO 3 ) [261]. The reaction between the metabolites in the plant extract then reduces the metal ions in solution, thus metal nanoparticles are produced [261]. The use of environmentally friendly plant extracts was discovered to generate a considerable number of AgNps using AgNO 3 as an inorganic metal [258]. Reported studies have found that AgNps exhibit significant antimicrobial activity and low toxicity to humans [258,265,266].
Recently, several AgNps investigations have been conducted using Tabernaemontana species, with T. divaricata being the most investigated species (Table 10). In the study by Devaraj et al. [256], various T. divaricata extracts were used for biosynthesis, and characterized, and assessed for cytotoxicity against MCF-7 cell lines. The analysis showed that the average particle size ranged from 22.85 nm and the biosynthesized nanoparticles showed potential cytotoxicity to human breast cancer cells (MCF-7) [256]. It is highly probable that these nanoparticles could be regularly used in various sectors, such as medical, cosmetic, and food applications [256]. In another study conducted by Anbukkarasi et al. [267], T. divaricata extracts were used for biosynthesizing nanoparticles and the resulting biosynthesized nanoparticles were tested in vivo to prevent the formation of cataracts in selenite-induced cataractogenesis in Wistar rat pups [267]. It was revealed that rats induced with AgNps treatment displayed a reduction in lenticular alterations compared to plant extract-treated rats [267]. The results of the study recommend that biosynthesized AgNps using T. divaricata extracts may provide limitations of selenite-induced cataractogenesis in vivo, while simultaneous sustaining standard lenticular calcium homeostasis by avoiding adjustments in important lenticular proteins [267].

Conclusions
The current review established an inclusive assessment of the major alkaloidal compounds within species belonging to the genus Tabernaemontana, which demonstrated pharmacological potential. The various secondary metabolites derived from Tabernaemontana species, such as terpenes, lactones, steroids, phenolics, flavonoids, and alkaloids, are often utilized in ethnobotany for their curative effects. Furthermore, these bioactive components have displayed numerous biological activities, including antimicrobial, antioxidant, anti-inflammatory, anticholinesterase, antineurodegenerative, anticancer, antidiabetic, antivenom, larvicidal, antihypertensive action, wound healing, and analgesic effects. However, despite the presence of biologically active chemical compounds within the genus Tabernaemontana, many species lack chemical and biological evaluation. Thus, further research is crucial to gain insight about the bioactive compounds and relative pharmacological activities of this esteemed genus.