1 Introduction

Terminalia Linn, comprising about 250 species in the world mostly as medium or large trees, is the second largest genus in the family Combretaceae. The name “Terminalia” is derived from Latin word “terminus”, which means the leaves are located at the tip of the branch. The bark of Terminalia plants usually has cracks and branches tucked into layers. Most of the Terminalia plants’ leaves are large, leathery with solitary or clustered small green white flowers. Their fruits are yellow, dark red or black; drupe, usually angular or winged. Some fruits are edible, highly nutritious and possess medicinal values.

Terminalia species are widely distributed in the southern Asia, Himalayas, Madagascar, Australia, and the tropical and subtropical regions of Africa. Terminalia plants in southern Asia have been intensively studied phytochemically due to their wide usage in Asian (India, Tibetan, and Chinese) traditional medicine systems [1]. For example, the fruits of Terminalia bellirica and Terminalia chebula, together with Phyllanthus emblica (Euphorbiaceae) which form the herbal remedy, Triphala, in Tibetan medicine, have received much attention because of its extensive and remarkable effectiveness in the treatment of anticancer, antifungal, antimicrobial, antimalarial, antioxidant.

So far, 39 Terminalia species have been investigated for their phytochemical constituents, which resulted in the identification of terpenes, tannins, flavonoids, lignans and simple phenols, amongst others. Pharmacological studies suggest that they have exhibited activity on liver and kidney protection, antibacterial, antiinflammatory, anticancer, and have displayed a positive effect on immune regulation, cardiovascular disease and diabetes, and acceleration of wound healing.

This paper features 39 important medicinal and edible Terminalia species and summarizes their traditional usage, geographical distribution, structures of isolated chemical constituents and pharmacological activities.

2 Species’ Description, Distribution and Traditional Uses

So far, 50 Terminalia species have been documented, 39 of which have been reported to possess medicinal properties and/or being edible. Among them, eight species and four varieties including T. argyrophylla, T. bellirica, T. catappa, T. chebula, T. franchetii, T. hainanensis, T. myriocarpa, T. intricate, T. chebula var. tomentella, T. franchetii var. membranifolia, T. franchetii var. glabra, and T. myriocarpa var. hirsuta are distributed in China (Yunnan, southeast Tibet, Taiwan, Guangdong, south Guangxi and southwest Sichuan). Their distribution and traditional applications are shown in Table 1.

Table 1 Local names, distributions and traditional uses of Terminalia plants
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Terminalia species are broadly used in many aspects. Some are employed as drugs, while others can provide high quality wood, tannin or dyes. For example, fruits of T. ferdinandiana, a species largely distributed in Australia, are rich in vitamin C, and possess strong antioxidant activity [25]. T. bellirica and T. chebula are not only recorded in every version of Chinese pharmacopoeia, but are also the important and most commonly applied drugs in Han, Tibetan, Mongolian and many other folk medicinal systems in India, Burma, Thailand, Malaysia, Vietnam and other southeast asian countries. T. catappa is a commonly used medicinal plant for liver protection in China [20].

3 Chemical Composition

Since 1930s, the chemical compositions of the genus Terminalia have been vastly studied. T. arjuna, T. bellirica, T. catappa and T. chebula, having been frequently used in the Ayurvedic, Chinese and Tibetan medicines, attracted scholars’ attention. To date, 368 compounds, largely terpenoids (1–104), tannins (105–196), flavonoids (197–241), lignans (242–265), phenols and glycosides (268–318) were reported from the genus (Tables 2, 3).

Table 2 Chemical constituents isolated from the genus Terminalia and the studied plant organs
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Table 3 The numbers and main types of compounds reported from different Terminalia species
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3.1 Terpenoids

So far, 104 terpenoids (Fig. 1) including 86 triterpenes (1–86), 14 monoterpenes (87–100), 4 sesquiterpenes (101–104) have been reported from the genus Terminalia. The triterpenoids are mainly oleanane, ursane and lupine types, and their glycosides. Particularly, Atta-ur-Rahman et al. isolated a new seco-triterpene terminalin A (81) possessing a novel rearranged seco-glutinane structure with a pyran ring-A and an isopropanol moiety from the stem barks of T. glaucescens [129]. Ponou et al. found two dimeric triterpenoid glucosides, ivorenosides A and B (49–50) possessing an unusual skeleton [131], and two new oleanane type triterpenes, 3-oxo-type ivorengenin A (41) and 3,24-dinor-2,4-secooleanane-type ivorengenin B (53) from the barks of T. ivorensis [132]. Compounds 41, 49 and 53 showed significant anticancer activities. Wang et al. isolated five new 18,19-secooleanane type triterpene glycosyl esters, namely arjunasides A–E (82–86) from the MeOH extract of T. arjuna’s barks, TaBs [68]. Moreover, five ursane type triterpene glucosyl esters (64–68) were also obtained for the first time [76]. From the fruits of T. chebula, 23-O-neochebuloylarjungenin 28-O-β-d-glycosyl ester (21) and 23-O-4′-epi-neochebuloylarjungenin (22) with novel substituents at C-23 were reported, in addition to compounds 23–24, 30–32 and 63, whose C-23 substituents were gallate. Compounds 30 and 31 had strong hypoglycemic effect [146]. Furthermore, compound 40 was obtained from the barks of T. arjuna [85], while friedelin (79) with 3-oxo moiety was reported from the fruits of T. arjuna [83], the root barks of T. avicennioides [93], and the stem barks of T. glaucescens [130] and T. mollis [35].

Fig. 1
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The structures of terpenoids 1–104

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3.2 Tannins

As the main secondary metabolites, 91 tannins (105–195) were reported from the genus Terminalia (Fig. 2), including ellagitannins, gallotannins, dimeric, and trimeric tannins. Four cinnamoyl-containing gallotannins (182–185) were discovered firstly from the fruits of T. chebula, and 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose (183) and 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl) ellagic acid (186) showed significant inhibitory activity on α-glucosidase with IC50 values of 2.9 and 6.4 μM, respectively [159].

Fig. 2
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The structures of tannins 105–195

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Tannins possess not only liver and kidney protection properties, but also anti-diarrhea, anticancer, antibacterial and hypoglycemic activities [133]. However, a condensed tannin terminalin (186) from T. oblongata was reported to have severe hepatorenal toxicity and even caused renal necrosis [39].

3.3 Flavonoids

The Terminalia genus are rich in flavonoids (Fig. 3) comprising of flavanones (196–202), flavones (203–215), flavan-3-ols (216–225), and flavonols (226–233). Among them, cerasidin (235) of chalcone, genistein (236) of isoflavone, and leucocyanidin (239) of flavan-3,4-diol from T. arjuna [80] were described as rare structural types in the Terminalia genus. Moreover, a new chalcone glycoside 2-O-β-glucosyloxy-4,6,2′,4′-tetramethoxychalchone (234) was reported from the roots of T. alata [53]. In addition, anthocyanidin cyanidin (237) and pelargonidin (238), flavanoid 7-hydroxy-3′,4-(methylenedioxy)flavan (240) and other structure were reported [12, 23, 66]. Compounds 209–213, 215 were C-glycosides at C-6 or C-8 of ring A.

Fig. 3
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The structures of flavonoids 197–240

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3.4 Lignans

Twenty-seven lignans (241–267) were reported from the genus Terminalia (Fig. 4). A new lignan 4′-O-cinnamoyl cleomiscosin A (248) was reported from the ethanol extract of T. tropophylla roots [72]. Moreover, 13 new furofuran lignan glucosides, terminalosides A–K (250–260), 2-epiterminaloside D (261), 6-epiterminaloside K (262) and 5 new polyalkoxylated furofuranone lignan glucosides, terminalosides L–P (263–267) were obtained from the leaves of T. citrina. All of them were tested for their estrogenic and/or antiestrogenic activities using estrogen responsive breast cancer cell lines T47D and MCF-7, and showed varying degrees of inhibitory activity. Among them, terminalosides B (251), G (256), L (263) and M (264) inhibited cell growth by up to 90% at a minimum concentration of 10 nM [22, 121].

Fig. 4
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The structures of lignans 241–267

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3.5 Phenols and Glycosides

There are 52 phenols and glycosides reported in the Terminalia genus (Fig. 5), in which ellagic acid (268) and gallic acid (289) are present in almost all species. Studies have shown that most of the simple phenolic compounds have antioxidant, antibacterial, hypoglycemic, liver and kidney protection [23].

Fig. 5
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The structures of phenols and glycosides (268–319)

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3.6 Sterols and Cardiac Glycosides

Only 6 sterols (320–325) and 2 cardiac glycosides (326-327) were isolated from the genus Terminalia before 2001 (Fig. 6).

Fig. 6
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The structures of steroids (320–325) and cardiac glycosides (326–327)

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3.7 Polyols and Esters

Polyols and lipids were reported to be abundant in the genus Terminalia and concentrated mainly in fruits and leaves [125]. So far, 9 polyol (328–336) and 6 esters (337–342) have been documented (Fig. 7).

Fig. 7
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The structures of polyols and esters (328–342)

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3.8 Other Compounds

Other compounds featured in the Terminalia genus are shown in Fig. 8 and are mostly styrenes. Cao et al. isolated two new cytotoxic xanthones - termicalcicolanone A (365), termicalcicolanone B (366) in T. calcicola, and found an inhibitory effect on ovarian cancer [19]. Hiroko Negishi et al. obtained a new chromone derivative - terminalianone (364) from the barks of Terminalia brownii [98]. Ansari et al. isolated the novel compound, 4′-substituted benzoyl-β-d glycoside (368), from the fruits of T. bellirica and illustrated its potential for anticoagulation [160].

Fig. 8
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The structures of other compounds (343–368)

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Moreover, chlorophyll and various vitamins were reported from the genus Terminalia.

4 Pharmacological Activities

The pharmacological activities of the genus Terminalia, mainly including antimicrobial, antioxidant, cytotoxicity, anti-inflammatory, hypoglycemic, cardiovascular, mosquitocidal and antiviral, have been extensively studied.

4.1 Antimicrobial

Extracts of several Terminalia species exhibit antimicrobial activity against various microbes. For example, methanol and aqueous extracts of T. australis were demonstrated antimicrobial activity against Ca. albicans (MIC = 180 and 250 µg/mL, resp.) and Ca. kruzzei (MIC = 250 and 300 µg/mL, resp.) [8]. Aqueous extracts of the stem barks, woods and whole roots of T. brownii showed antibacterial activity against standard strains of Sta. aureus (14.0 ± 1.1 µg/mL), Escherichia coli, Ps. aeruginosa (12.0 ± 1.1 µg/mL), Klebsiella pneumonia (6.0 ± 1.0 µg/mL), Sa. typhi and Bacillus anthracis (13.0 ± 1.0 µg/mL), as well as fungi Ca. albicans (12.3 ± 1.5 µg/mL) and Cr. neoformans (9.7 ± 1.1 µg/mL) [16]. Ethanol extracts of the root barks and leaves of T. schimperiana were against Sta. aureus, Ps. aeruginosa and Sa. typhi (MIC = 0.058–2.089 mg/mL), with inhibition zone diameters (IZDs) of 17.2 to 10.0 mm, compared to gentamicin (IZD = 21.8–10 mm). The results supported the efficacy of the extracts in the folkloric treatment of burns wounds, bronchitis and dysentery, respectively [42]. Antibacterial tests on Mycobacterium smegmatis ATCC 14468 showed that methanol extract of T. sambesiaca roots and stem barks had promising effects (MIC = 1.25 mg/mL, both) [133].

Ellagitannin punicalagin (133) obtained from the stem barks of T. mollis demonstrated crucial activity against Ca. parapsilosis and Ca. krusei (MIC = 6.25 μg/mL), as well as Ca. albicans (MIC = 12.5 μg/mL) [35]. 7-Hydroxy-3′,4′-(methylenedioxy) flavan (240), termilignan (241), anolignan B (242) and thannilignan (243) isolated from the fruit rinds of T. bellirica displayed significant antifungal activity against Penicillium expansum (MIC = 1.0, 2.0, 3.0 and 4.0 µg/mL, resp.), also with 240 and 241 against Ca. albicans at 10 and 6 µg/mL, resp. [12]. The antimycobacterial activity of friedelin (79) furnished from the root barks of T. avicennioides was 4.9 μg/mL in terms of MIC value [93]. β-Arjungenin (16), betulinic acid (74), sitosterol (319) and stigmasterol (323) from T. brownii were proved to possess antibacterial activity, with 74 the most active against A. niger and S. ipomoea (MIC = 50 μg/ml) [99].

4.2 Antioxidant

Terminalia species have also illustrated some interesting antioxidant properties [161]. By a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, relatively high anti-oxidant activities of the methanol extracts of T. alata, T. bellirica and T. corticosa trunk-barks were found (IC50 = 0.24, 1.02 and 0.25 mg/mL, resp.), compared to the positive control, l-ascorbic acid (IC50 = 0.24 mg/mL) [2].

Flavonoid glycosides, apigenin-6-C- (211) and apigenin-8-C- (212) (2″-O-galloy1)-β-d-glucoside, isolated from dried fallen leaves of T. catappa, showed significant antioxidative effects (IC50 = 2.1 and 4.5 µM, resp.) on Cu2+/02-induced low density lipoprotein lipid peroxidation, with probucol (IC50 = 4.0 µM) as positive control [105].

Arjunaphthanoloside (351), isolated from the stem barks of T. arjuna showed potent antioxidant activity and inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages [87], while ivorenosides B (51) and C (52), two triterpenoid saponins from T. ivorensis, exhibited scavenging activities against DPPH and ABTS+ radicals [131].

The antioxidant potential of T. paniculata (TPW) was investigated by DPPH, ABTS2−, NO, superoxide (O2−), Fe2+ chelating and ferric reducing/antioxidant power (FRAP) assays. TPW showed maximum superoxide, ABTS2−, NO, DPPH inhibition, and Fe2+-chelating property at 400 µg/mL, resp. FRAP value was 4.5 ± 0.25 µg Fe(II)/g, which demonstrated the efficacy of aqueous barks extract of T. paniculata as a potential antioxidant and analgesic agent [142].

TaB contains various natural antioxidants and has been used to protect animal cells against oxidative stress. The alleviating effect of TaB aqueous extract against Ni toxicity in rice (Oryza sativa L.) suggested that TaB extract considerably alleviated Ni toxicity in rice seedlings by preventing Ni uptake and reducing oxidative stress in the seedlings [162]. Behavioral paradigms and PCR studies of TaB extract against picrotoxin-induced anxiety showed that TaB supplementation increased locomotion towards open arm (EPM), illuminated area (light–dark box test), and increased rearing frequency (open field test) in a dose dependent manner, compared to picrotoxin (P < 0.05). Furthermore, alcoholic extract of TaB showed protective activity against picrotoxin in mice by modulation of genes related to synaptic plasticity, neurotransmitters, and antioxidant enzymes [174].

4.3 Cytotoxicity

70% Acetone extracts of T. calamansanai leaves inhibited the viability of human promyelocytic leukemia HL-60 cells. Sanguiin H-4 (115), 1-α-O-galloylpunicalagin (136), punicalagin (135), 2-O-galloylpunicalin (147) and methyl gallate (290) were the main components isolated from T. calamansanai with the IC50 values of 65.2, 74.8, 42.2, 38.0 and > 100 µM, respectively, for HL-60 cells. Apoptosis of HL-60 cells treated with 1-α-O-galloylpunicalagin, 115, 135, and 147 was noted by the appearance of a sub-G1 peak in flow cytometric analysis and DNA fragmentation by gel electrophoresis. 115 and 147 induced a decrease of the human poly (ADP-ribose) polymerase (PARP) cleavage-related procaspase-3 and elevated activity of caspase-3 in HL-60 cells, but not normal human peripheral blood mononuclear cells, PBMCs [18].

Terminaliaside A (60), an oleanane-type triterpenoid saponin isolated from the roots of T. tropophylla showed antiproliferative activity against the A2780 human ovarian cancer cell line with an IC50 value of 1.2 µM [72]. The 70% methanolic extract of T. chebula fruits was found to decrease cell viability, inhibit cell proliferation, and induce cell death of human (MCF-7) and mouse (S115) breast cancer, human osteosarcoma (HOS-1), human prostate cancer (PC-3) and a non-tumorigenic, immortalized human prostate (PNT1A) cell lines. Flow cytometry and other analyses showed that some apoptosis was induced by the extract at lower concentrations, but at higher concentrations, necrosis was the major mechanism of cell death. Chebulinic acid (143) and ellagic acid (186) were tested by ATP assay on HOS-1 cell line in comparison with three known antigrowth phenolics of Terminalia, gallic acid (287), methyl gallate (290), luteolin (206), and tannic acid (169). Results showed that the most growth inhibitory phenolics in T. chebula fruits were chebulinic acid (IC50 = 53.2 µM ±/0.16) >/tannic acid (IC50 = 59.0 mg/mL ±/0.19) > ellagic acid (IC50 = 78.5 µM ±/0.24) [111].

Aqueous and ethanolic extracts of T. citrina fruits were revealed to exhibit significant mutagenicity in tested strains of baby hamster kidney cell line (BHK-21). Ethanolic extract showed higher mutagenicity in TA 100 strain, whereas aqueous extract exhibited higher mutagenicity in TA 102 strain than TA 100. Both extracts showed dose-dependent mutagenicity. Fifty percent cell viability was exhibited by 260 and 545 μg/mL of ethanolic and aqueous extracts respectively [169]. Moreover, ivorenoside A (50) showed antiproliferative activity against MDA-MB-231 and HCT116 human cancer cell lines with IC50 values of 3.96 and 3.43 µM, respectively [131].

4.4 Anti-inflammatory

Inflammation has been considered as a major risk factor for various kinds of human diseases. Macrophages play substantial roles in host defense against infection. It can be activated by LPS, the major component of the outer membrane of Gram-negative bacteria. An investigation was carried out to determine anti-inflammatory potential of ethyl acetate fraction isolated from T. bellirica (EFTB) in LPS stimulated RAW 264.7 macrophage cell lines. EFTB (100 μg/mL) inhibited all inflammatory markers in dose dependent manner. Moreover, EFTB down regulated the mRNA expression of TNF-α, IL-6, COX-2 and NF-κB against LPS stimulation. These results demonstrated that EFTB is able to attenuate inflammatory response possibly via suppression of ROS and NO species, inhibiting the production of arachidonic acid metabolites, proinflammatory mediators and cytokines release [165].

Anolignan B (242) isolated from roots of T. sericea was tested for anti-inflammatory activity using the cyclooxygenase enzyme assays (COX-1 and COX-2) It showed activity against both COX-1 (IC50 = 1.5 mM) and COX-2 (IC50 = 7.5 mM) enzymes [151]. Termiarjunosides I (47) and II (48) isolated from stem barks of T. arjuna inhibited aggregation of platelets and suppressed the release of NO and superoxide from macrophages [156].

The anti-inflammatory activities of a polyphenol-rich fraction (TMEF) obtained from T. muelleri was assessed using carrageenan-induced paw edema model by measuring PGE2, TNF-α, IL-1b, and IL-6 plasma levels as well as the paw thickness. The group treated with 400 mg/kg of TMEF showed a greater inhibition in the number of writhes (by 63%) than the standard treated group (61%). TMEF pretreatment reduced the edema thickness by 48, 53, and 62% at the tested doses, respectively. TMEF administration inhibited the carrageenan-induced elevations in PGE2 (by 34, 43, and 47%), TNF-α (18, 28, and 41%), IL-1β (14, 22, and 29%), and IL-6 (26, 31, and 46%) [166].

4.5 Hypoglycemic

Some species and isolates from Terminalia have indicated possession of α-glucosidase inhibitory capabilities. Gallic acid (287) and methyl gallate (290), from stem barks of T. superba, showed significant activity (IC50 = 5.2 ± 0.2 and 11.5 ± 0.1 μM, resp.). Arjunic acid (5) and glaucinoic acid (46) from stem barks of T. glaucescens showed significant β-glucuronidase inhibitory activity with IC50 value 80.1 and 500 μM, resp., against β-glucuronidase [130].

In a study to investigate α-glucosidase inhibition of extracts and isolated compounds from T. macroptera leaves, chebulagic acid (142) showed an IC50 value of 0.05 µM towards α-glucosidase and 24.9 ± 0.4 µM towards 15-lipoxygenase (15-LO), in contrast to positive controls (acarbose: IC50 = 201 ± 28 µM towards α-glucosidase, quercetin: IC50 = 93 ± 3 µM towards 15-LO). Corilagin (116) and narcissin (231) were good 15-LO and α-glucosidase inhibitors. Rutin (230) was a good α-glucosidase inhibitor (IC50 ca. 3 µM), but less active towards 15-LO [136].

From the fruits of T. chebula, 23-O-galloylarjunolic acid (30) and 23-O-galloylarjunolic acid 28-O-β-d-glucosyl ester (31) were afforded and showed potent inhibitory activities with IC50 values of 21.7 (30) and 64.2 (31) µM, resp., against Baker’s yeast α-glucosidase, compared to the positive control, acarbose (IC50 174.0 µM) [146].

Hydrolyzable tannins, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose (183) and 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl) ellagic acid (186) from the fruits of T. chebula, showed significant α-glucosidase inhibitory activities with IC50 values of 2.9 and 6.4 µM, resp. In addition, inhibition kinetic studies showed that both compounds have mixed-type inhibitory activities with the inhibition constants (Ki) of 1.9 and 4.0 µM, respectively [159].

4.6 Cardiovascular

A few species of Terminalia have demonstrated cardiovascular activities. It was reported that the barks of T. arjuna possessed significant inotropic and hypotensive effect, mild diuretic, antithrombotic, prostaglandin E2 enhancing and hypolipidaemic activities [66].

Ethanolic extract of T. pallida fruits (TpFE) were studied to determine their cardioprotection against isoproterenol (ISO)-administered rats. The supplementation of TpFE dose-dependently exerts notable protection on myocardium by virtue of its strong antioxidant activity. It could be used as a medicinal food for the treatment of cardiovascular ailments [163].

4.7 Mosquitocidal

Insect-borne diseases remain to this day a major source of illness and can cause death worldwide. The resistance to chemical insecticides among mosquito species has been a major problem in vector control. The larvicidal and ovicidal activities of crude benzene, hexane, ethyl acetate, chloroform and methanol extracts of T. chebula were tested for their toxicity against three important vector mosquitoes, viz., Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus. All extracts showed moderate larvicidal effects, the highest larval mortality was found in the methanol extract of T. chebula against the larvae of A. stephensi, A. aegypti, and C. quinquefasciatus with the LC50 values of 87.13, 93.24 and 111.98 ppm, respectively. Mean percent hatchability of the ovicidal activity was observed 48 h post treatment. All the five solvent extracts showed moderate ovicidal activity. The maximum egg mortality (zero hatchability) was observed in the methanol extract of T. chebula at 200 and 250 ppm against A. stephensi, while A. aegypti and C. quinquefasciatus showed 100% mortality at 300 ppm. No mortality was observed in the control group. The finding of the investigation revealed that the leaf extract of T. chebula possesses remarkable larvicidal and ovicidal activity against medically important vector mosquitoes [167, 168].

4.8 Antiviral

Termilignan (241) and anolignan B (242), obtained from T. bellirica exhibited antimalarial activity against the chloroquine-susceptible strain 3D7 of Plasmodium falciparum (IC50 = 9.6 ± 1.2 μM)[12]. Casuarinin (129), chebulagic acid (142) from the fruits of T. chebula possessed hepatitis C virus inhibition activities (IC50 = 9.6 and 5.2 μM, resp.) [118]. Punicalin (128) and 2-O-galloylpunicalin (147), isolated from aqueous extract of T. triflora leaves, showed inhibitory activity on HIV-1 reverse transcriptase with IC50 of 0.11 μg/mL (0.14 μM) and 0.10 μg/mL (0.11 μM), resp. [149].

In vitro anti-HIV-1 activity of acetone and methanol extracts of T. paniculata fruits was studied by Durge A. et al. Cytotoxicity tests were conducted on TZM-bl cells and PBMCs, the CC50 values of both extracts were ≥ 260 μg/mL. By using TZM-bl cells, the extracts were tested for their ability to inhibit replication of two primary isolates HIV-1 (X4, Subtype D) and HIV-1 (R5, Subtype C). The activity against HIV-1 primary isolate (R5, Subtype C) was confirmed by using activated PBMC and quantification of HIV-1 p24 antigen. Both the extracts showed anti-HIV-1 activity in a dose-dependent manner. The EC50 values of the acetone and methanol extracts of T. paniculata were ≤ 10.3 μg/mL. Furthermore, the enzymatic assays were performed to determine the mechanism of action which indicated that the anti-HIV-1 activity might be due to inhibition of reverse transcriptase (≥ 77.7% inhibition) and protease (≥ 69.9% inhibition) enzymes [172].

Kesharwani A. et al. investigated anti-HSV-2 activity of T. chebula extract and its constituents, chebulagic acid (142) and chebulinic acid (143). Cytotoxicity assay using Vero cells revealed CC50 = 409.71 ± 47.70 μg/mL for the extract whereas 142 and 143 showed more than 95% cell viability up to 200 μg/mL. The extract from T. chebula (IC50 = 0.01 ± 0.0002 μg/mL), chebulagic (IC50 = 1.41 ± 0.51 μg/mL) and chebulinic acids (IC50 = 0.06 ± 0.002 μg/mL) showed dose dependent in vitro anti-viral activity against HSV-2, which can also effectively prevent the attachment and penetration of the HSV-2 to Vero cells. In comparison, acyclovir showed poor direct anti-viral activity and failed to significantly (p > 0.05) prevent the attachment as well as penetration of HSV-2 to Vero cells when tested up to 50 μg/mL. Besides, in post-infection plaque reduction assay, T. chebula extract, chebulagic and chebulinic acids showed IC50 values of 50.06 ± 6.12, 31.84 ± 2.64, and 8.69 ± 2.09 μg/mL, resp., which were much lower than acyclovir (71.80 ± 19.95 μg/mL) [173].

4.9 Others

Terminalia species were also reported to be used in the treatment of diarrhea [95], Alzheimer’s disease [112], psoriasis [164], liver disease [170], kidney disease [171], etc. Terminalosides A–K (249–259) from the leaves of the Bangladeshi medicinal plant T. citrina possess estrogen-inhibitory properties. Among them, Terminaloside E (253) showed inhibitory activity against the T47D cell line, such terminalosides C (252), F (255), and I (258). Besides, 6-epiterminaloside K (262) displayed antiestrogenic activity against MCF-7 cells [22].

5 Conclusion and Future Prospects

The genus Terminalia contains not only a large number of tannins, simple phenolics, but also a lot of terpenoids, flavonoids, lignans and other compounds. Most tannins, simple phenolics and flavonoids have antioxidation, antibacterial, antiinflammatory and anticancer activities. The plants of the genus Terminalia have exhibited positive effect on immune regulation, cardiovascular disease and diabetes, and can accelerate wound healing [157]. Therefore, the Terminalia genus has great medicinal potential. However, most of the chemical composition of species is still unknown, we should use modern advanced technology such as LC–MS to continue to isolate its compounds, and determine their pharmacological activities and mechanism of action, to explore other possible greater medicinal value.