The Progress of Anti-HBV Constituents from Medicinal Plants in China
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Hepatitis B virus (HBV) infection causing acute and chronic hepatitis is a serious problem worldwide, whereas the current treatment methods are unsatisfactory. Traditional Chinese herbs that have long been used for medicinal purposes are fascinating sources for novel anti-HBV candidates. This paper summarizes the progress of anti-HBV constituents from diverse medicinal plants in China to provide information for searching new anti-HBV drugs from natural sources.
KeywordsHepatitis B virus Anti-HBV activity Medicinal plants HBsAg HBeAg HBV DNA
Hepatitis B infection caused by the hepatitis B virus (HBV) can become either acute or chronic diseases. HBV infections are among the top ten causes of death, and lead to 0.89 million deaths every year. It is estimated that 257 million people are living with chronic HBV infection. China is one of the high prevalence areas accounting for one-third of the infections. The major complications of chronic hepatitis B (CHB) are cirrhosis and hepatocellular carcinoma (HCC) [1, 2]. Hepatitis B vaccination is effective in preventing HBV infections; however, it is invalid to those who have already been infected with HBV. Interferons and nucleoside analogs are the most common drugs for CHB in clinic. Interferons (INF-α and PegIFN-α) take effects by enhancing the immune system of patients, but their application is limited by the low curing rate and serious side effects. Nucleoside analogues (mainly lamivudine, adefovir dipivoxil, telbivudine, entecavir, tenofovir disoprox and clevudine) can inhibit HBV replication by targeting on viral DNA polymerase; however, the drug-resistance and relapse are challenging after long-term treatment [3, 4, 5]. Currently, there is no cure for CHB, and new treatment methods with unprecedented targets are urgently needed. Traditional Chinese herbs that have long been used for medicinal purpose in China are fascinating sources for anti-HBV candidates [6, 7]. This paper summarized the progress of anti-HBV constituents from medicinal plants in China.
2 Active Constituents from Medicinal Plants
According to the traditional Chinese medicine (TCM) theory, CHB is characteristic with the syndrome of liver stagnation and spleen deficiency. Thus, traditional Chinese herbs with the properties of “clearing heat removing dampness” and “promoting blood circulation and removing blood stasis” are preferable in searching anti-HBV candidates.
2.1 Artemisia Plants
Plants of Artemisia contain about 300 species mainly present in the temperate, cold temperate and subtropical regions of Asia, Europe and North America. One hundred and eighty six Species and 44 variants are distributed in China, many of which are used as medicinal herbs. Yin-Chen is a famous TCM that has been used to treat jaundice in China for thousands of years. The first application of Yin-Chen could be traced back to the first Chinese dispensatory, “Shen-Nong-Ben-Cao-Jing”. Two species, namely Artemisia capillaris (Yinchenhao) and Artemisia scoparia (Binhao), are documented in Chinese Pharmacopoeia as the authentic resources of Yin-Chen. According to the bioassay on HepG 2.2.15 cell line in vitro, the 90% ethanol extract of A. capillaris exhibited activity against the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 value of 460.33 μg/mL (SI = 1.4), 295.31 μg/mL (SI = 2.5) and 49.13 μg/mL (SI = 13.4), respectively. Detailed LCMS analyses on the active part showed the presence of a series of chlorogenic acids. Subsequent isolation gave rise to chlorogenic acid (1), cryptochlorogenic acid (2), neochlorogenic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), chlorogenic acid methyl ester (7), cryptochlorogenic acid methyl ester (8) and neochlorogenic acid methyl ester (9). Chlorogenic acid analogues (1–3) showed activity against HBV DNA replication with IC50 values of 5.5 (SI > 250.1), 13.7 (SI > 115.0) and 7.3 (SI > 249.9) μM; dicaffeoyl analogues (4–6) significantly inhibited HBV DNA replication with IC50 values of 6.4 μM (SI > 256.1), 9.8 μM (SI > 184.8) and 6.1 μM (SI > 184.8), as well as moderate activity against the secretions of HBsAg and HBeAg; the methylated analogues (7–9) dramatically decreased the activity against HBV DNA replication, with IC50 values of 272.3 (SI > 6.2), 175.3 (SI > 11.2) and 144.7 (SI > 20.2) μM, respectively. This result revealed the anti-HBV active constituents of A. capillaris and provided valuable information for the potential use of chlorogenic acid analogues as novel non-nucleoside anti-HBV candidates. Furthermore, seven new enynes, 8-(Z)-decene-4,6-diyne-1,3,10-triol (10), 1,3S,8S-trihydroxydec-9-en-4,6-yne (11), and 3S,8S-dihydroxydec-9-en-4,6-yne 1-O-β-d-glucopyranoside (12), 8S-deca-9-en-4,6-diyne-1,8-diol (13), (S)-deca-4,6,8-triyne-1,3-diol (14), 3S-hydroxyundeca-5,7,9-triynoic acid (15), 3S-hydroxyundeca-5,7,9-triynoic acid 3-O-β-d-glucopyranoside (16), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-β-d-glucopyranose (17), together with 34 known compounds were also obtained from this plant. Most of the isolates showed good to moderate activity, and especially, pumilaside A could inhibit both the secretions of HBsAg and HBeAg and HBV DNA replication with IC50 values of 15.02 μM (SI = 111.3), 9.00 μM (SI = 185.9) and 12.01 μM (SI = 139.2); protocatechuic acid and caffeic acid exhibited inhibition on HBV DNA replication with IC50 values of 32.60 (SI > 255.8) and 16.83 (SI > 255.6) μM; Compound 16 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) μM [8, 9, 10, 11].
In order to characterize the anti-HBV constituents of A. scoparia, the bioassay in vitro suggested that the 90% ethanol extract showed inhibition on the secretions of HBsAg and HBeAg with inhibition rates of 36.5 ± 8.1 and 25.0 ± 6.7% (1 mg/mL), and HBV DNA replication with inhibition rate of 49.3 ± 9.7% (0.25 mg/mL). As a result, three new compounds, 4-pyridoneglucoside (18), 3S,8S-dihydroxydec-9-en-4,6-yne 1-O-(6′-O-caffeoyl)-β-d-glucopyranoside (19) and 3S,8S-dihydroxydec-9-en-4,6-yne 1-O-(2′-O-caffeoyl)-β-d-glucopyranoside (20) were obtained from the active part under the guidance of LCMS analyses. 4-Pyridoneglucoside (18) is an unusual 4-pyridone glucoside that could inhibit the secretions of HBsAg and HBeAg with IC50 values of 0.61 mM (SI = 2.1) and 0.88 mM (SI = 1.4), respectively, and HBV DNA replication with an IC50 value of 0.47 mM (SI = 2.7). Compound 19 displayed inhibition on HBV DNA replication with an IC50 value of 0.07 mM (SI = 23.6), and compound 20 showed slightly decreased activity with an IC50 value of 0.12 mM (SI = 17.1) .
2.2 Swertia Plants
Plants of the genus Swertia (Gentianaceae) are annual or perennial herbs, which are mainly distributed in Asia, Africa and North America. Of the total 170 species, 79 species and 10 variants are present in China. There are about 30 Swertia plants are used as medicinal herbs in treating hepatitis, cholecystitis, pneumonia, osteomyelitis, dysentery and scabies. The detailed investigation on Swertia plants is valuable for searching new anti-HBV candidates.
Swertia leducii (Mengzi Zhangyacai) is an annual herbaceous plant mainly distributed in Mengzi County of the Yunnan Province. Many traits of S. leducii are similar to those of S. mileensis, except for petioles and flowers. Due to their close morphology, S. leducii was always used as the alternative for S. mileensis in producing “Qing-Ye-Dan” medicines. In order to clarify the anti-HBV constituents, a pair of novel enantiomeric lactones, (±)-sweriledugenin A (54, 55), were isolated from S. leducii under the guidance of LCMS investigation. Both (+)- and (−)-sweriledugenin A showed activities inhibiting HBV DNA replication with IC50 values of 36.86 (SI = 10.5) and 26.55 (SI = 31.6) μM on the HepG 2.2.15 cell line in vitro . This investigation is a valuable attempt for guided isolation from a completed natural complex.
Swertia punicea (Zihong Zhangyacai), the congener species of S. mileensis, are used for the treatment of hepatitis in the folk of Yunnan Province. The anti-HBV screening manifested that the EtOAc extract of S. punicea showed inhibitory activities on HBsAg and HBeAg with IC50 values of 0.69 and 0.15 mg/mL, respectively. In order to clarify the active components, swerpunilactone A (56) and its plausible precursors, (±)-gentiolactone (58) and bellidifolin (59) were isolated from the whole plants of S. punicea. Simultaneously, swerpunilactone B (57), (±)-gentiolactone, and norbellidifolin (60) were further obtained from S. hispidicalyx and S. yunnanensis. Swerpunilactones A and B as two unusual xanthone and secoiridoid heterodimers showed similar activity inhibiting HBsAg secretion with IC50 values of 0.25 (SI = 1.2) and 0.29 (SI > 1.4) mM, and HBV DNA replication with IC50 values of 0.18 (SI > 1.7) and 0.19 (SI > 2.2) mM. Bellidifolin could obviously inhibit HBV DNA replication with an IC50 value of 0.09 (SI > 10.9) mM. Norbellidifolin showed inhibition on both HBsAg and HBeAg secretions and HBV DNA replication with IC50 values of 0.77 (SI > 6.2), < 0.62 (SI > 7.8) and 0.58 (SI > 8.3) mM, respectively . This is the first report of xanthone and secoiridoid heterodimers connected with C–C bond.
Swertia kouitchensis (Guizhou Zhangyacai), a perennial herb mainly distributed in Southern China, is widely used as a fork medicine to treat jaundice, indigestion and sore throat. Detailed investigation on the ethanol part of S. kouitchensis yielded three new secoiridoids, swertiakoulactone (71) and swertiakosides A and B (72, 73), as well as 28 known compounds. Swertiakoside B is a new secoiridoid glycoside in which the glycosyl is attached to the aglycon by the OH-1′ and OH-2′ simultaneously. Swertiakoulactone showed moderate activities inhibiting the HBsAg secretion (IC50 = 1.10 mM, SI = 4.4) and HBV DNA replication (IC50 = 1.16 mM, SI = 4.1) [27, 28].
Swertia cincta (Xinan Zhangyacai), the congener plant of S. mileensis, is generally used to treat hepatitis in the folk region of Yunnan Province (China). The in vitro anti-HBV bioassay manifested that the 90% ethanol extract of S. cincta could inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 151.5 μg/mL (SI > 20.0), 53.7 μg/mL (SI > 40.8) and 121.9 μg/mL (SI > 24.0), respectively. In order to clarify its active constituents, extensive investigation on the ethanol extract of S. cincta yielded six new compounds, including five secoiridoid glycosides, swericinctosides A and B (74–75), 9-epi-swertiamarin (76), 2′-O-mhydroxybenzoyl swertiamarin (77), 4″-O-acetyl swertianoside E (78), and one unusual lactone enol ketone, 3-(hydroxymethyl ene) dihydro-2H-pyran-2,4(3H)-dione (79), as well as 18 known ones. The most active swertiaside (80) exhibited activity against HBV DNA replication with an IC50 value of 0.05 mM (SI = 29.1), as well as moderate activity against HBsAg secretion (IC50 = 0.79 mM, SI = 2.0). Swericinctosides A and 9-epi-swertiamarin also showed moderate activity inhibiting HBsAg secretion with IC50 values of 0.32 and 1.06 mM, and HBV DNA with IC50 values of 0.46 and 0.62 mM, respectively [29, 30].
Swertia angustifolia (Xiaye Zhangyacai), the congener plant of S. mileensis, is used for treating hepatitis and cholecystitis in the folk region of Yunnan Province (China). The phytochemical investigation on this plant gave rise to seven new secoiridoids, swertianglide (81) and swertianosides A–F (82–87), together with 29 known compounds. Swertianoside A, an unusual secoiridoid glycoside dimer with two molecules of secoiridoids connected with a glucosyl group, showed significant activities inhibiting the secretions of HBsAg (IC50 = 0.18 mM, SI = 3.1) and HBeAg (IC50 = 0.12 mM, SI = 4.7), and HBV DNA replication (IC50 = 0.22 mM, SI = 2.5). As a comparison, other secoiridoid glycosides displayed no activity or cytotoxicity at the tested concentration. This result suggests the importance of two secoiridoid aglycones in the structure [31, 32].
Swertia mussotii (Chuanxi Zhangyacai) is a well-known Tibetan folk medicine (Zangyinchen) to treat hepatitis. According to the preliminary bioassay in vitro, the ethanol extract of S. mussotii showed significant inhibitory activity on the secretions of HBsAg and HBeAg with IC50 values of 0.55 mg/mL (SI = 2.1) and 0.19 mg/mL (SI = 6.2), respectively, and HBV DNA replication with an IC50 value of 0.043 mg/mL (SI = 27.2). Subsequent investigation on the active part gave rise to 69 compounds, involving two new xanthones, 8-O-β-d-glucopyranosyl-1-hydroxy-2,3,5-trimethoxyxanthone (93) and 8-O-[β-d-xylopyranosyl-(1 → 6)-β-d-glucopyranosyl]-1-hydroxy-2,3,5-trimethoxyxanthone (94), and seven new secoiridoids, (−)-swermusic acids A (95) and B (96), and (−)-swerimuslatone A (97), four new secoiridoid glycosides, 6′-O-formylsweroside (98), 6′-O-formylgentiopicroside (99), 6′-O-acetylamarogentin (100) and 6′-O-acetylamaronitidin (101), and two new linear monoterpenes, swerimusic acids C (102) and D (103). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses. Eight xanthones exhibited significant activity inhibiting HBV DNA replication with IC50 values from 0.01 to 0.13 mM. Especially, mangiferin and isoorientin could inhibit HBV DNA replication with IC50 values of 0.01 (SI > 145.2) and 0.02 (SI > 177.0) mM, respectively. This is the first time to systematically investigate the xanthones and their anti-HBV activity in Swertia plants. Ethyl 3,4-dihydroxybenzoate and ethyl 2,5-dihydroxybenzoate also showed inhibition on HBsAg secretion with IC50 values of 0.14 (SI > 41.6) and 0.23 (SI > 32.3) mM; 2-C-β-d-glucopyranosyl-1,3,7-trihydroxyxanthone could suppress HBeAg secretion with an IC50 value of 0.04 mM (SI = 47.8) [35, 36, 37].
Swertia patens (Xiejing Zhangyacai), mainly distributed in Yunnan and Sichuan provinces of China, is used as a folk medicine to treat hepatitis in folk. However, its chemical constituents and bioactivities were seldom reported. In continuing efforts to discover anti-HBV active compounds from Swertia, phytochemical investigation on S. patens led to the isolation of two new secoiridoids, swerpatic acid (104) and swerpalactone (105), together with 28 known compounds. Swerpatic acid (106) is an unusual C8-skeleton secoiridoid aglycone. Two known compounds, (+)-dehydrodiconiferyl alcohol and dehydrozingerone showed moderate activities inhibiting the secretion of HBsAg with IC50 values of 1.94 mM (SI = 1.1) and 0.50 mM (SI = 2.9), while other compounds exhibited obvious cytotoxicity on Hep G 2.2.15 cell with CC50 values from 0.24 to 2.06 mM [38, 39].
Swertia chirayita (Yindu Zhangyacai) is distributed throughout the temperate Himalaya area. The whole plant is widely used by local people for the treatment of hepatitis, inflammation and digestive diseases. Based on the preliminary bioassay in vitro, the EtOH extract showed inhibition on the secretions of HBsAg and HBeAg with IC50 values of 1.08 mg/mL (SI > 2.0) and 0.11 mg/mL (SI > 19.6), and HBV DNA replication with an IC50 value of 0.17 mg/mL (SI = 12.9). Bioassay-guided fractionation of the active part resulted in four new compounds, swertiachiralatone A (89), swertiachoside A (107), swertiachirdiol A (108) and swertiachoside B (109), together with 26 known ones. All the isolates were evaluated for their anti-HBV activity on HepG 2.2.15 cells in vitro. Four compounds showed activity inhibiting HBsAg secretion; two compounds showed activity inhibiting HBeAg secretion; and nine compounds exhibited activity inhibiting HBV DNA replication. In particular, 1-hydroxy-3, 7-dimethoxyxanthone (110) displayed obviously inhibition on HBV DNA replication with an IC50 value of 0.16 mM (SI > 12.4). (+)-Cycloolivil-4′-O-β-d-glucopyranoside (111) exhibited inhibiting on the secretions of HBsAg and HBeAg with IC50 values of 0.31 mM (SI = 4.3) and 0.77 mM (SI = 1.8), and HBV DNA replication with an IC50 value of 0.29 mM (SI = 4.7) . This work provides valuable information for understanding the anti-HBV active constituents of S. chirayita.
Swertia hispidicalyx (Maoe Zhangyacai) is mainly distributed in Tibet of China and Nepal. The first study on the ethanol part gave rise to 11 compounds, two of which showed anti-HBV activity. In particular, 1,5,8-trihydroxy-3-methoxyxanthone (112) showed potent activity against HBeAg secretion with an IC50 value of 0.35 mM (SI > 2.8) and HBV DNA replication with an IC50 value of 0.09 mM (SI > 10.9) .
Swertia delavayi (Lijiang Zhangyacai) known as “Gan-Yan-Cao” or “Zou-Dan-Cao” is distributed in northwestern Yunnan and southern Sichuan of China. This plant is widely used as a fork medicine for treating jaundice, hepatitis and cholecystitis in Tibetan and Naxi medicines. According to the preliminary bioassay in vitro, the ethanol extracts of S. delavayi exhibited significant inhibition on the secretions of HBsAg and HBeAg with IC50 values of 1.64 mg/mL (SI = 2.3) and 1.13 mg/mL (SI = 3.6), and HBV DNA replication with an IC50 value of 0.34 mg/mL (SI > 7.3). As a continuous search for anti-HBV active constituents from natural sources, 15 compounds were obtained from the active part of this plant. Especially, isovitexin (113) exhibited significant activity inhibiting HBV DNA replication with an IC50 value of 0.05 (SI = 19.8) mM, and the secretion of HBeAg with an IC50 values of 0.23 (SI = 4.3) mM .
2.3 Other Plants
Alisma orientalis (Zexie) is widely cultivated in China and Japan, and its dried rhizomes are famous crude drugs for the treatment of diabetes and diuretics. In order to characterize the anti-HBV active constituents, detailed investigation on this plant yielded two new sesquiterpenes, alismorientols A (115) and B (116), one new protostane-type triterpene, alisol O (117), and seven known ones, alisol A (118), alisol A 24-acetate (119), 25-anhydroalisol A (120), 13β,17β-epoxyalisol A (121), alisol B 23-acetate (122), alisol F (123) and alisol F 24-acetate (124). Anti-HBV bioassay on HepG 2.2.15 cell line in vitro revealed that alismorientol A exhibited inhibition on the secretions of HBsAg and HBeAg, with IC50 values of 1.1 (SI = 16.7) and 14.7 (SI > 1.2) μM, respectively. Seven protostane-type triterpenes (118–124) showed potent anti-HBV activity, and especially, alisol F 24-acetate could inhibited the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) secretions with IC50 values of 7.7 (SI = 18.5) and 5.1 (SI = 28.0) μM [45, 46]. This is the first time to reveal the anti-HBV active constituents of A. orientalis.
Illicium henryi (Honghuixiang) is a shrub distributed in the southwestern part of China, and its bark and roots have been used as a folk-medicinal herb for dispelling wind-evil and assuaging pain. In order to characterized the active constituents, detailed investigation on the stems and roots of I. henryi yielded 39 compounds, involving 7 new ones. The structures of the new compounds were elucidated as dihydrodehydrodiconiferyl alcohol 9-O-β-d-(3″-O-acetyl)-xylopyranoside (151) and threo-4,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan 7-O-α-rhamnopyranoside (152) and henrylactones A–E (153–157) by extensive spectroscopic analyses and X-ray diffraction experiment. Most of the new lignans displayed anti-HBV property, especially (−)-dihydrodehydrodiconiferyl alcohol (158) showed moderate activity inhibiting both HBsAg and HBeAg secretions with IC50 values of 0.06 (SI = 8.8) and 0.53 (SI = 1.1) mM, respectively. For the sesquiterpenes, tashironin A (159) showed an IC50 value of 0.48 mM (SI = 6.3) in inhibiting HBsAg secretion, and 0.15 mM (SI = 20.1) in inhibiting HBeAg secretion. Henrylactones A–E (153–157) also showed moderate activity inhibiting HBsAg secretion with IC50 values ranging from 0.098 to 1.85 mM, and HBeAg with IC50 values ranging from 0.24 to 2.91 mM [50, 51, 52].
Pericampylus glaucus (Xiyuanteng), a climbing shrub, is widely distributed in southwest China, whose roots are used for treating laryngitis, cough and pulmonary disease, and leaves are applied for fractures and boar bites. Detailed investigation on the ethanolic extract of P. glaucus yielded four new alkaloids, periglaucines A–D (162–165), along with three known ones, norruffscine (166), (−)-8-oxotetrahydropalmatine (167) and (−)-8-oxocanadine (168). Compounds 162–167 showed anti-HBV activity on HepG2.2.15 cell line in vitro. The most potent compound 167 could inhibit HBsAg secretion with an IC50 value of 0.14 mM (SI = 22.4) .
Radix Astragali (Huangqi), one of the most widely prescribed Chinese medicines, is the dried root of Astragalus membranaceus (FISCH.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. The major saponin astragaloside IV (185) effectively suppressed the secretions of HBsAg and HBeAg with inhibition rates of 23.6 and 22.9% at 100 mg/mL. Furthermore, astragaloside IV showed 64.0% inhibition to serum DHBVs at 120 mg/kg .
Rheum palmatum (Zhangye Dahuang) is a famous traditional Chinese herb with antibacterial, anticancer and antiviral properties. Li et al. reported two anthraquinones, emodin (186) and rhein (187) showing inhibition on HBV DNA with an IC50 value of 10.48 and 9.89 μg/mL .
Saniculiphyllum guangxiense (Biandouyecao) the only species of the genus Saniculiphyllum (Saxifragaceae), is a perennial herb mainly distributed in Yunnan and Guangxi provinces of China. The first phytochemical investigation resulted in the isolation of two new triterpenoids, 16β-hydroxybryodulcosigenin (188) and 3α-O-feruloylolean-12-en-27-oic acid (189), together with six known compounds. The nitrile glucoside, menisdaurin (190), showed potent activity inhibiting HBV DNA replication with an IC50 value of 0.32 mM (SI > 12.0) [63, 64].
Scutellaria baicalensis (Huangqin) is a widely used Chinese herbal medicine in antiinflammatory and anticancer therapy. The main constituent, wogonin (191), from this plant showed potent anti-HBV activity both in vitro and in vivo. Wogonin could inhibit HBsAg and HBeAg with an IC50 value of 4 μg/mL, and DHBV DNA polymerase with an IC50 value of 0.57 μg/mL .
Sophora flavescens (Kushen) widely distributed throughout China is commonly used the treatment of skin diseases and gynecological diseases. Quinolizidine alkaloids are the characteristic constituents in this plant from which Chen et al. reported one new, (+)-12α-hydroxysophocarpine, and ten known quinolizidine alkaloids. (+)-Oxysophocarpine (192), (−)-sophocarpine (193), (+)-lehmannine (194), (−)-13,14-dehydrosophoridine (195) could significantly inhibited HBsAg secretion by more than 48.3% and HBeAg secretion by 24.6–34.6% at the noncytotoxic concentration of 0.2 lmol/mL. The preliminary SARs suggest the importance of double bond in ring D .
3 Conclusion and Perspective
This paper summarized the progress of anti-HBV constituents from medicinal plants in China. In total, 198 compounds involving monoterpenes, sesquiterpenes, triterpenes secoiridoids and their polymers, alkaloids, xanthones, lignans, enynes, amides and polyphenols were reviewed. Especially, four secoiridoid trimers, swerilactones H–K can obviously suppress HBV DNA replication with IC50 values ranging from 1.53 to 5.34 μM, comparable to the positive drug lamivudine (3TC). With the consideration of the novel structures, they should have different action mechanism with nucleosides. Oxymatrine has been used to treat hepatitis B in clinic with confirmed efficiency and safety, and its target is host Hsc70 instead of viral polymerase. Thus, natural products from traditional Chinese herbs will provide prolific candidates for searching new anti-HBV drugs with diverse mechanisms.
Hepatitis B as a type of chronic hepatitis is accompanied with high levels of alanine transaminase (ALT) and aspartate transaminase (AST). In addition to anti-HBV efficiency, TCMs can reduce the ALT and AST levels by improving the hepatic function of patients, and relieve HBV-associated clinical symptoms, e.g. anorexia, hypodynamia, nausea and vomiting, to improve the life quality of patients. Thus, TCMs maybe have advantages in treating HBV infection with multi-component and multi-target properties. Although, TCMs are fascinating sources for anti-HBV candidates, the complicated constituent and time-consuming isolation restrict the following drug development. Chemical modification on active natural products is an effective method in searching for anti-HBV agents, which can rapidly yield plenty of candidates from the starting substrates, and rationally increase the bioactivity, decrease the toxicity, or improve their physicochemical properties under the guidance of SARs.
This work was financially supported by the Program of Yunling Scholarship, the Youth Innovation Promotion Association, CAS, the Applied Basic Research Programs of Yunnan Province (2017FB137), the CAS Hundred Talents Program, and the CAS “Light of West China” Program (Western Youth Scholars “A”).
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflict of interest.
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