The Chemical Constituents Of Three Kadsura Medicinal Plants And Their Bioactivities

About 10 species of the Kadsura genus, belonging to Schisandraceae family, are recorded to distribute in China, mostly in the South-West and South-East parts. The stems and roots of these plants have been often used as traditional Chinese medicine or folk medicine in the south of China to treat rheumatic arthritis, traumatic injury, gastric and duodenal ulcer, dysmenorrheal, abdominal pain, and related diseases. Many studies were carried out about the species of Kadsura distributing in the South-West. Meanwhile, more and more lignans and triterpenes from Kadsura were reported to exhibit various beneficial activities such as anti-HBeAg, antihepatotoxic, antitumor, anti-HIV, and anti-lipid-peroxidative. Enhance, lots of studies focused on discovering novel structures and new activities from Kadsura recently. However, the resources of some species such as K. oblongifolia, K. japonica and etc. were not so clear, and the chemical constituents of these species were not reported either. In order to discover the resources, and to elucidate the bioactive principles of these medical plants, an investigation of the resources of Kadsura in Fujian province, and some phytochemical works were carried out.97 compounds have been isolated by CC, PTLC, recrystallization, and identified by UV, IR, MS,1H-NMR,13C-NMR, DEPT, 2D-NMR, CD. They belong to lignan, triterpene, steroid, benzene derivative, flavonoid, alkaloid and fatty acid, respectively.10 of them are new compounds.In the investigation,5 species of kadsura were found in Fujian province. According to the morphological characteristic, they were identified as K. coccinea, K. longipedunculata, K. heteroclita, K. japonica and K. oblongifolia. So, it was confirmed that there were abundant resource of K. japonica, K. oblongifolia and K. coccinea in Fujian. This finding is not only to give some beneficial complementarity to the Flora of China, but also to afford the experimental materials for further research.Phytochemical investigation into the ether soluble extract of the stems and roots of K. oblongifolia collected in XianYou of Fujian, led to the isolation and identification of 50 compounds, including 26 lignans,11 triterpenes (1 nortriterpene),1 flavonoid (KO-25) and 1 alkaloid (KO-300). Among the 26 lignans, maily are dibenzoeyelooctadienes such as kadsufolins A-E (KO-10, KO-13, KO-35, KO-26, KO-38)、kadsurin (KO-3)、schisantherin F (KO-5)、kadsurarin (KO-7)、schizanrin F (KO-8)、heteroclitin B (KO-9)、angeloyl-binankadsurin A (KO-23)、angeloyl-binankadsurin B (KO-27)、acetyl-binankadsurin A (KO-43) and so on,2 of them are spirobenzofuranoid dibenzocyclooctadienes known as kadsulignan G (KO-49) and kadsulignan F (KO52-2),2 of them are diarylbutanes, named meso-dihydroguaiaretic acid (KO-21) and kadsufolin F (KO-30),1 of them is neolignan, named licarin A (KO-12).11 triterpenes (including its derivatives and nortriterpene) were identified as schizandronic acid (KO-4)、kadsulactone (KO-6)、3-ethoxy-3-oxo-9,19-cyclo-3,4-secolanosta-4,24-dien-26-oic acid 22,26- lactone (KO-28)、3-ethoxy-3-oxo-9,19-cyclo-3,4-secolanosta-4(28),24-dien-26-oic acid 22,26-lactone (KO-29)、kadsudilactone (KO-22)、seco-neokadsuranic acid (KO-47)、nigranoic acid (KO-53)、3,4-seco(24Z)-cycloart-4(28),24-diene-3,26- dioic acid 3-methyl ester (KO-54)、mangiferonic acid (KO-14)、manwuweizic acid (KO-17) and oblongifolactone (KO-52).5 dibenzoeyelooctadiene lignans named kadsufolin A (KO-10), B (KO-13), C (KO-35), D (KO-26), E (KO-38), respectively,1 diarylbutane lignan named kadsufolin F together with 1 nortriterpene named oblongifolactone (KO-52) are 7 new compounds. Moreover,41 known compounds are isolated from this plant for the first time. Among them,3,4-seco(24Z)-cycloart-4(28),24-diene-3,26-dioic acid 3-methyl ester (KO-54) and aurantiamide acetate (KO-300) are the first time isolated from the Schisandraceae family.From the ether soluble extract of the stems and roots of K. japonica collected in MinHou of Fujian,25 compounds were isolated, including 13 lignans and 6 triterpenes. Among the 13 lignans,3 are tetrahydroforans, known as chicanine (KJ-47), (R)-tran-3,4-dipiperonyl-tetrahydro- furan (KJ-21) and d-epigalbacine (KJ-22); 7 are dibenzoeyelooctadienes, such as kadsurin (KJ-65) kadsurindutin B (KJ85-2)、wuweizisu C (KJ100-4) and deoxychidandrin (KJ65-2), and so on; 3 diarylbutanes, are identified as 3-methoxyl-4-hydroxyl-3’,4’-methenedioxyl lignin (KJ-40), meso-dihydroguaiaretic acid (KJ-85) and (±)-dihydro-cubebin (KJ21-1); 2 are spirobenzofuranoid dibenzocyclooctadienes named as isointeriotherin D (KJ100-2) and heteroclitin H (KJ100-1). Isointeriotherin D (KJ100-2) is a new compound possessing a rather new structure, which was rarely studied. In addition,17 known compounds are the first time isolated from this plant.Totally 22 compounds were isolated from the stems and roots of K. coccinea collected in ShunChang of Fujian, including 8 lignans,10 triterpenes, and 4 other compounds. Among the 8 lignans,3 are diarylbutanes, named kadsufolin F (HLH20-2)、3-methoxyl-4-hydroxyl-3’,4’-methenedioxyl lignin (HLH-2) and sauriol B (HLH20-3); 2 dibenzoeyelooctadienes, named schisantherin F (HLH-17) and neokadsuranin (HLH-15)、2 are spirobenzofuranoid dibenzocyclooctadienes, known as kadsulignan D(HLH-20) and kadsulignan G (HLH21-1); the other one is tetrahydroforan, identified as d-epigalbacine (HLH-1). The 10 triterpenes were identified as 2 novel triterpenes named coccinetaneⅠ(HLH-9) and coccilactone (HLH-21) together with 8 known compounds, named kadsulactone (HLH-4) changnanic acid (HLH21-2)、renchanglactone A (HLH22-2)、schizandronic acid (HLH-6) 3-ethoxy-3-oxo-9,19-cyclo-3,4-secolanosta-4,24-dien-26-oic acid 22,26-lactone (HLH20-7)、schisanlactone E (HLH20-1)、schisanlactone B (HLH22-1) and kadsulactone A (HLH-22), respectively.2 new compounds and 9 known compounds are isolated from this plant for the first time.The compounds isolated from the three Kadsura plants mentioned above, were selected to evaluate the bioactivities.Anti-HBV bioassays were performed with 21 compounds. Among them, renchanglactone A was found to show significant antiviral effect on hepatitis B virus in vitro with inhibitory potency against HBsAg secretion at 59.5%, IC50 value 131.1μg/mL, angeloyl-binankadsurin A showed inhibitory potency against HBeAg secretion at 51.85%, IC50 valuable 48.0μg/mL. It seems that, the phenolic hydroxyl at 1-position should be important to the anti-HBV activity, for dibenzoeyelooctadiene lignans.Anti-HIV bioassays were performed with 53 compounds, yet, none of them showed significant effect at 4μg/mL.52 compounds were tested in vitro against a panel of human tumor cell lines such as A549 (lung carcinoma), DU145 (prostate carcinoma), HCT-8 (ileocecal carcinoma), KB (epidermoid carcinoma of the nasopharynx) and KBvin (drug-resistant KB).11 lignans including kadsufolin A, kadsufolin D, together with 4 triterpenes including schizandronic acid were found to show cytotoxicity against A549, DU145, HCT-8, KB and KBvin cell lines in vitro, with GI50 values of 3.9-20.0μg/mL. It seems that, the methylenedioxy, phenolic hydroxyl would have some influences on the activities of dibenzoeyelooctadiene lignans, and the group at the 3- position might determine the activities of triterpenes.10 lignans and 11 triterpenes were tested in the classic pathway of anti-complementary activity. Nigranoic acid, manwuweizic acid and schizandronic acid inhibited anti-complement activity with CH50 values of 0.90-1.17 mg/mL.As a conclusion, it was confirmed that K. japonica, K. oblongifolia and K. coccinea were distributing in Fujian. Totally,97 compounds including 40 lignans,18 triterpenes,1 flavonoid and 1 alkaloid and some other compounds were isolated from the K. oblongifolia, K. japonica and K. coccinea. Among them,7 lignans and 3 rtriterpenes are new compounds. Four compounds including renchanglactone A and angeloyl-binankadsurin A showed inhibitory potency against HBV.16 compounds including kadsufolin A, kadsufolin D and kadsulactone showed cytotoxicity, and 3 compounds nigranoic acid, manwuweizic acid and schizandronic acid showed anti-complement activity. The results of this investigation were expected to complement the phytotaxonomy and to enrich the database of natural products; to offer both phytochemical and biological activity proofs to chemtaxonomy; to afford important academic basis for the exploitation and utilization of natural resources and to supply a significant scientific basis for pharmacology, chemotaxonomy and screening of new medicines.