Discovery of nontriterpenoids from the rot roots of Panax notoginseng with cytotoxicity and their molecular docking study and experimental validation.

Panax notoginseng (PN) is a well-known traditional Chinese medicine, with dammarane-type triterpenoid saponins characterized as major component and active ingredients, together with amino acids, flavonoids, polysaccharides, and polyacetylenes. The roots of PN are susceptible to root rot disease, which causes a huge loss and changes in the chemical components of this precious resource. In this study, sub-fractions of rot PN root extracts were preliminarily found to have admirable cytotoxicity on two human cancer cells. Further bioassay-guided isolation discovered nine new non-triterpenoids, including two novel N-methylacetamido-1-oxotetrahydropyrimidine alkaloids (1, 2), five 2H-furanones or 2H-pyranones (3-7), and two polyacetylenic alcohols (8, 9). Their structures were illuminated by extensive spectroscopic data, calculated ECD, and X-ray diffraction analysis. Among them, 3-7 were considered to be transformed from panaxatriol through the intermediates (8, 9). The new alkaloids (1, 2) displayed noteworthy cytotoxicity against five human cancer cells with IC50 values ranging from 14 to 24 µM. In silico target prediction and molecular docking studies showed that 1 and 2 may interact with EGFR, and were verified by the experimental inhibitory effect on EGFR tyrosine kinase.

New ent-Kaurane and cleistanthane diterpenoids with potential cytotoxicity from Phyllanthus acidus (L.) Skeels.

Six diterpenoids including three ent-kauranes (1-2, 4) and three cleistanthanes (3, 5-6) were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels. Of them, (16S)-ent-16,17,18-tri-hydroxy-19-nor-kaur-4-en-3-one (1), phyllanthone A (2), and 6-hydroxycleistanthol (3) are new compounds, while the ent-kaurane diterpenoids were reported from the titled plant for the first time. Their structures were elucidated on the basis of the extensive spectroscopic analyses. Compounds 2 and 4-6 displayed cytotoxic potential with IC50 values ranging from 1.96 to 29.15 µM. They also showed moderate anti-inflammatory activities (IC50 = 6.30-12.05 µM). Particularly, the new ent-kaurane 2 displayed cytotoxic potential against HL-60 (IC50 = 2.00 µM) and MCF-7 (IC50 = 3.55 µM) cells, and anti-inflammatory activity (IC50 = 6.47 µM).

Phyllaciduloids E and F, two new cleistanthane diterpenoids from the leaves of Phyllanthus acidus.

Phyllaciduloids E (1) and F (2), two new cleistanthane diterpenoids, were isolated from the leaves of Phyllanthus acidus (L.) Skeels (Phyllanthaceae). Their planar structures were established by spectroscopic analysis and comparison with literature values. The relative configurations of phyllaciduloids E and F were confirmed by DFT-NMR chemical shift calculations and subsequent CP3 probability methods. Phyllaciduloids E and F were evaluated for their cytotoxicity. However, no significant activities were detected at concentrations up to 40 µM.[Formula: see text].

New cytotoxic dichapetalins in the leaves of Phyllanthus acidus: Identification, quantitative analysis, and preliminary toxicity assessment.

The young leaves of Phyllanthus acidus (Euphorbiaceae) are commonly used as edible vegetables in Indonesia, Thailand, and India, and their water infusions as dieting aids for people trying to remain slim. However, it is regarded as a poisonous plant in Malaya, and current researches are insufficient to provide a conclusion on its toxicity and safety under large doses. In this study, we firstly found that the refined nonpolar extracts of P. acidus leaves showed significant cytotoxic effect against BEAS-2B and L02 normal cell lines with IC50 values of 2.15 and 1.64 mg/mL, respectively. Further bioactivity-guided isolation produced four new rare dichapetalins (pacidusins A-D) from the most active fraction. Their structures including absolute configurations were elucidated by extensive spectroscopic data and X-ray diffraction analysis. All the isolated dichapetalins exhibited moderate cytotoxicity against, BEAS-2B and L02 normal cell lines with IC50 values ranging from 12.44 to 22.55 µM, as well as five human cancer cell lines with IC50 values ranging from 3.38 to 22.38 µM. Furthermore, the content of the main dichapetalins in the leaves were determined by analytical HPLC, which showed that the leaves contained a very high amount of the four isolated dichapetalins with a total yield of 0.488 mg/g of dry plant material. These toxic dichapetalins may lead to adverse health effects in higher doses. Our findings indicate that the dichapetalin containing leaves may not be suitable for consumption in large quantities as food, but demonstrate their potency as anti-cancer agents for new drug discovery.

Multiple in vitro biological effects of phenolic compounds from Terminalia chebula var. tomentella.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia chebula (TC), a well-known Indian Ayurvedic medicine introduced into China in the Sui and Tang Dynasties, has been recorded and used medicinally as Fructus Chebulae, together with its variety tomentella (TCT) in the Chinese Pharmacopoeia. They have been also used commonly for the treatment of diabetes mellitus by Tibetan medicine. AIM OF THE STUDY: To investigate the main bioactive and therapeutic principles in the fruits of TCT, based on the extensive evaluation of their anti-inflammatory and hypoglycemic activities. MATERIALS AND METHODS: The TCT fresh fruits were analyzed by HPLC and separated further by column chromatography and preparative HPLC. The isolated compounds were identified by extensive spectroscopic analyses, including 1D/2D NMR, MS, UV, IR and ECD. Anti-inflammatory activity was evaluated by inhibition of NO production in RAW264.7 cells. The specific iNOS (PDB ID: 3E7G) structure was prepared by Discovery Studio 4.0, and the molecular docking simulation was performed on GOLD (version 5.2.2). Hypoglycemic activity was measured using the substrate solution of 4-nitrophenyl-α-d-glucopyranoside enzyme and buffer solution. RESULTS: The HPLC analysis method of polyphenols in the fruits of TCT was established, and 13 main chromatographic peaks were identified, including six hydrolyzable tannins (2, 4-7, 10-11), three simple phenols (12-14), and one oleanane pentacyclic triterpene, arjungenin. Extensive chromatographic separation of TCT fresh fruits yielded 14 compounds, including one new natural hydrolyzable tannin, 2,3-(S)-HHDP-6-O-galloyl-d-glucose (1). The known compounds were identified as 10 hydrolyzable tannins (2-11) and three simple phenols (12-14). Compounds 10 (IC50 = 36.43 ± 0.21 µM), 11 (IC50 = 42.28 ± 0.09 µM) displayed stronger NO inhibitory activity than the positive control L-NMMA (IC50 = 42.34 ± 0.66 µM), while 2, 4, and 9 showed moderate inhibitory activity against NO production. Further molecular docking simulation of specific iNOS on 10 and 11, as well as five previously isolated lignans 15-19 showed that there were no obvious rules between docking results and the in vitro NO inhibitory activity for hydrolyzable tannins (10 and 11), while the mechanism of anti-inflammatory activity for lignans was related to the substitution of conjugated aldehyde groups. Moreover, most of the hydrolyzable tannins (1-2, 4-5, 9-11) and simple phenol (12) displayed stronger inhibitory effects on α-glucosidase than the positive control, quercetin (IC50 = 6.118 ± 0.071 µM), with IC50 values ranging from 0.079 to 16.494 µM. Among these bioactive isolates, the hydrolyzable tannins 2, 4-5, and 9-11, and simple phenol 12 are major chemical components in TCT fruit. CONCLUSIONS: The results showed that lignans and hydrolyzed tannins are the main active ingredients of TCT fruits, responsible for the traditional treatment of sore throat and cough. Moreover, hydrolyzed tannins and simple phenolic compounds with potential hypoglycemic activity are closely related to the ethno-pharmacological uses of TCT fruits on diabetes in Tibetan medicine.

Previously undescribed pyridyl-steroidal glycoalkaloids and 23S,26R-hydroxylated spirostanoid saponin from the fruits of Solanum violaceum ortega and their bioactivities.

Three previously undescribed pyridyl-steroidal glycoalkaloids, solanindiosides A‒C, one rare 23S,26R-hydroxylated spirostanoid saponin, and two steroidal alkaloid aglycones, solanindins A and B, derived from the acid hydrolysis of solanindiosides A‒C, were isolated from the fruits of Solanum violaceum, together with five known analogues, including two rare steroidal glycosides, two lignans and a diterpene. Structurally, they comprise a 16ß-methoxy-23-deoxy-22,26-epimino-cholest-type skeleton moiety, and a 16ß-methoxy-3,23-dideoxy-22,26-epimino-cholest-3,5-dien derivative. The hitherto undescribed structures were established on the basis of extensive spectroscopic analyses. Configurations of sugar moieties were resolved by chemical derivations. Solanindiosides A‒C, (22R,23S,25R,26R)-spirost-5-ene-3ß,23,26-triol3-O-ß-d-xylopyranosyl-(1→3)-ß-d-glucopyranoside, solanindins A and B, and (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol were evaluated for their cytotoxic and antibacterial activities. (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol showed the most potent cytotoxic activity against MCF-7 cells (IC50 = 4.386 ± 0.098 µM), while solanindin B displayed some inhibitory effects against Staphylococcus aureus Rosenbach with MIC50 value of 37.32 ± 0.793 µM. In addition, (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol induced dose dependent apoptosis effect in MCF-7 cells.

Phyllanthacidoid U: a new N-glycosyl norbisabolane sesquiterpene from Phyllanthus acidus (L.) skeels.

A novel highly oxygenated norbisabolane sesquiterpene, namely phyllanthacidoid U (1), along with nine known sesquiterpenes (2-10) was isolated from the roots and stems of Phyllanthus acidus (L.) Skeels (Phyllanthaceae), collected from Xishuangbanna, Yunnan province, China. Their structures were elucidated by means of extensive spectroscopic analysis and by comparison of their data with reported values in literatures. Instead of the C-13 ester O-glycosyl found mostly in the titled plant growing in Thailand, compound 1 possessed a rare N-ß-glucosamine-2-N-acetate moiety linked directly to the carbonyl at C-13 through an amido bond. Moreover, the acyl group at C-10 in 1 was (Z)-2-(2-hydroxyethyl)-pent-2-enedioyl group, instead of benzoic or p-hydroxybenzoic moieties found commonly in the reported norbisabolane sesquiterpenes. The known sesquiterpene 5 displayed stronger anti hepatitis B virus (HBV) activity with IC50 values of 1.69 ± 0.22 and 2.79 ± 0.69 µM towards HBV surface antigen (HBsAg) and HBV excreted antigen (HBeAg) secretion, respectively.

Phyllanacidins A-C, three new cleistanthane diterpenoids from Phyllanthus acidus and their cytotoxicities.

Phytochemical investigation on the nonpolar extracts of P. acidus leaves afforded three new cleistanthane diterpenoids, named phyllanacidins A-C (1-3), in addition to three known ones (4-6). Among them, compounds 2 and 3 represent the first examples of 17-nor cleistanthane diterpenoids. Their structures including absolute configurations were elucidated on the basis of extensive spectroscopic data and single crystal X-ray diffraction analysis. All the isolated cleistanthane diterpenoids were evaluated for their cytotoxic activities against five human cancer cell lines. Compounds 4-6 exhibited moderate cytotoxicity with IC50 values ranging from 16.11 to 30.82 µM.

New Flavoalkaloids with Potent α-Glucosidase and Acetylcholinesterase Inhibitory Activities from Yunnan Black Tea 'Jin-Ya'.

As a subgroup of flavoalkaloids, N-ethyl-2-pyrrolidinone substituted flavan-3-ols are reported to possess various biological activities that may play important roles in the beneficial healthcare functions of tea. The HPLC and LC-MS analyses showed the existence of N-ethyl-2-pyrrolidinone substituted flavan-3-ols in 'Jin-Ya', which is a Yunnan black tea produced only from the buds of the tea plant Camellia sinensis var. assamica. Further phytochemical study on this precious black tea led to the identification of 8 flavoalkaloids, 1-8, along with 11 known flavan-3-ols (9-14) and flavonol glycosides (15-19). The new compounds, (-)-6-(5″S)-N-ethyl-2-pyrrolidinone-epiafzelechin (1), (-)-8-(5″R)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2a), and (-)-8-(5″S)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2b), were identified based on extensive spectroscopic analysis. Flavoalkaloids 2-6 showed inhibitory activity on α-glucosidase with IC50 values ranging from 2.09 to 8.47 µM, compared to those of quercetin and acarbose (IC50 = 6.87 and 228.9 µM, respectively). Moreover, compounds 2, 3, and 6 displayed an inhibitory effect on acetyl-cholinesterase with IC50 values of 14.23, 33.79, and 34.82 µM, respectively, compared to tacrine (IC50 = 0.223 µM).

Steaming Changes the Composition of Saponins of Panax notoginseng (Burk.) F.H. Chen That Function in Treatment of Hyperlipidemia and Obesity.

Saponins of Panax notoginseng (Burk.) F.H. Chen have been classified as a type of composition in functional foods for numerous diseases. However, its mild effects and other characteristics limited clinical applications in diseases. Inspired by "nine steaming and nine processing" of P. notoginseng in traditional Chinese medicine, we developed a "steaming"-mimic protocol, which significantly changed the composition of saponins of P. notoginseng from the original, R1, Rg1, Re, Rb1, and Rd (raw-PNS), to the products after steaming, 20S/R-Rh1, Rk3, Rh4, 20S/R-Rg3, Rk1, and Rg5 (N-PNS). Surprisingly, N-PNS demonstrated promising activities in improving hyperlipidemia and reducing body weight and weight of white adipose tissue and the inhibition of adipogenesis in obese mice. In accordance with the results in vivo, N-PNS remarkably blunted adipogenesis at the early stage of differentiation dose-dependently in vitro. Moreover, we demonstrated that the activity may involve the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway by promoting phosphorylation of AMPKT172 and downregulating its downstream factors: sterol regulatory element binding protein 1c, stearoyl-CoA desaturase 1, and fatty acid synthase. Taken together, the steaming-induced eight compositions of saponins showed a very promising function in improving hyperlipidemia and obesity both in vivo and in vitro, providing fundamental evidence for future study and application in treatment of hyperlipidemia, obesity, and other lipid-related metabolic syndromes.

Termitomenins A-E: Five new lignans from Terminalia chebula var. tomentella (Kurz) C. B. Clarke.

An elaborated phytochemical study on the fresh fruits of Terminalia chebula var. tomentella (Combretaceae) led to the isolation of five new lignans, including three tetrahydrofuran (1-3) and two furofuran (4 and 5) derivatives, namely termitomenins A-E (1-5), along with 10 known ones. All of them were obtained from the titled plant for the first time. Their structures were determined by extensive spectroscopic analysis, including 1D/2D NMR, MS, UV, IR, electronic circular dichroism (ECD), time-dependent density functional theory (TDDFT) calculation of ECD spectra, and single crystal X-ray diffraction in case of 3. Compounds 1-15 exhibited certain anti-inflammatory activities. Interestingly, compounds 6 (IC50 = 18.17 ± 0.57  µM) and 7 (IC50 = 13.66 ± 0.38 µM) which contain an aldehyde group displayed stronger NO inhibitory activity than the positive control L-NMMA (IC50 = 42.34 ± 0.66 µM).

Triterpenoid saponins with hepatoprotective effects from the fresh leaves of Metapanax delavayi.

The fresh leaves of Metapanax delavayi (Araliaceae) have been used as a common wild vegetable for salad and soup, and also herbal tea by the local people living in its growing areas of Yunnan province, China. Detailed chemical investigation led to the identification of a new triterpenoid saponin, 3-O-α-L-arabinopyranosyl-28-O-ß-D-glucopyranosyl-(1→6)-O-ß-D-glucopyranosyl-3ß-hydroxyolean-12-ene-28,29-dioic acid (1) from the fresh leaves, together with 11 known compounds, including six triterpenoid saponins (2-7), two caffeoylquinic acid derivatives (8-9), and three flavonoid glycosides (10-12). Their structures were determined on the basis of spectroscopic analysis and acidic hydrolysis. Compounds 3-5 and 8-12 were isolated from M. delavayi for the first time. Moreover, the known saponins 3-O-ß-D-xylopyranosyl-3ß-hydroxyolean-12-ene-28,29-dioic acid (3) and yiyeliangwanoside IV (5) exhibited protective effects on HepG2 cells damaged by the alcohol intakes, at a concentration of 1.0 µg/mL. The results indicated M. delavayi is an ideal dietary vegetable and herbal tea with potential hepatoprotective activity.[Formula: see text].

The Genus Terminalia (Combretaceae): An Ethnopharmacological, Phytochemical and Pharmacological Review.

Terminalia Linn, a genus of mostly medium or large trees in the family Combretaceae with about 250 species in the world, is distributed mainly in southern Asia, Himalayas, Madagascar, Australia, and the tropical and subtropical regions of Africa. Many species are used widely in many traditional medicinal systems, e.g., traditional Chinese medicine, Tibetan medicine, and Indian Ayurvedic medicine practices. So far, about 39 species have been phytochemically studied, which led to the identification of 368 compounds, including terpenoids, tannins, flavonoids, phenylpropanoids, simple phenolics and so on. Some of the isolates showed various bioactivities, in vitro or in vivo, such as antitumor, anti HIV-1, antifungal, antimicrobial, antimalarial, antioxidant, diarrhea and analgesic. This review covers research articles from 1934 to 2018, retrieved from SciFinder, Wikipedia, Google Scholar, Chinese Knowledge Network and Baidu Scholar by using "Terminalia" as the search term ("all fields") with no specific time frame setting for the search. Thirty-nine important medicinal and edible Terminalia species were selected and summarized on their geographical distribution, traditional uses, phytochemistry and related pharmacological activities.

New anti-HBV norbisabolane sesquiterpenes from Phyllantus acidus.

The norbisabolane-type sesquiterpenoids bearing a spiroketal functionality have been found in Phyllanthus spp. and showed anti-HBV activities. As part of an ongoing effort to search for promising anti-HBV sesquiterpenes from Phyllanthus plants, we report four new norbisabolane-type sesquiterpenoids, phyacidusin A (1), phyacidusin B (2), phllanthacidoid A1 (3) and phllanthacidoid N1 (4), from stem of P. acidus collected in Xishuangbanna, Yunnan province, China. The absolute configuration of new compounds was established by coupling constants and ROESY correlations, as well as comparation of NMR data with those of known compounds. The absolute configuration of new compounds 1 and 2 was further confirmed by X-ray diffraction. Compound 2 showed effect to HBsAg with an IC50 value of 11.2 ±â€¯0.01 µM, while compound 3 inhibited HBeAg secretion with an IC50 value of 57.1 ±â€¯0.02 µM. The results enriched the diversity of anti-HBV norbisabolane sesquiterpenes.

GC-MS-based identification and statistical analysis of liposoluble components in the rhizosphere soils of Panax notoginseng.

Continuous cropping obstacle, mainly caused by microorganisms and organic components in soil, has become a serious problem for the plantation of Panax notoginseng (Araliaceae) due to the rapidly increased demands of this famous herbal medicine in recent decades. The rhizosphere soils cultivated with 3-year-old healthy and ill notoginseng were chemically investigated by gas chromatography-mass spectrometry (GC-MS) and compared with the corresponding soils without the plantation of notoginseng. Totally 47 liposoluble components were identified. Furthermore, the multiple statistical analysis showed that these constituents were qualitatively and quantitatively associated with the differences between the cultivated soil with P. notoginseng and the uncultivated soil. Among them, neophytadiene (4), d-α-tocopherol (38), (3ß,22E,24S)-ergosta-5,22-dien-3-ol (39), (3ß,24R)-ergost-5-en-3-ol (40), stigmasta-5,22-dien-3-ol (41), stigmast-4-en-3-one (44) and (5α)-stigmastane-3,6-dione (47) contributed most to the significant differences between the cultivated and uncultivated soils, whereas cyclopentadecane (3), octadecanoic acid methyl ester (16), docosanoic acid ethyl ester (31), nonacosane (34), 38 and 39 were found in much higher amount in the soils with ill P. notoginseng as compared to the case of those with the healthy P. notoginseng. On the other hand, liposoluble components in different cultivation areas were of great diversity; however, they were able to remain relatively consistent across the overall trend of differential substances.

Plant Resources, Chemical Constituents, and Bioactivities of Tea Plants from the Genus Camellia Section Thea.

Tea, as one of the most popular beverages with various bioactivities, is commonly produced from the fresh leaves of two widely cultivated tea plants, Camellia sinensis and C. sinensis var. assamica. Both plants belong to the genus Camellia section Thea, which was considered to have 12 species and 6 varieties according to Min's taxonomic system. Most species, except the cultivated species, are known as wild tea plants and have been exploited and utilized to produce tea by the local people of its growing areas. Thus far, six species and varieties have been phytochemically studied, leading to the identification of 398 compounds, including hydrolyzable tannins, flavan-3-ols, flavonoids, terpenoids, alkaloids, and other phenolic and related compounds. Various beneficial health effects were reported for tea and its components, involving antioxidant, antitumor, antimutagenic, antidiabetic, hypolipidemic, anti-inflammatory, antimicrobial, antiviral, antifungal, neuroprotective, hepatoprotective, etc. In this review, the geographical distribution of tea plants and the chemical constituents (1-398) reported from the genus Camellia section Thea and some tea products (green, black, oolong, and pu-erh tea) that have ever been studied between 1970 and 2018 have been summarized, taking species as the main hint, and the main biological activities are also discussed.

Research of Panax spp. in Kunming Institute of Botany, CAS.

Panax, a genus of the Araliaceae family, is an important herbal group in traditional Chinese medicine (TCM). Nine species and three varieties are included in the genus of Panax, in which nearly all species have been used for medicinal purposes. Among them, Panax notoginseng (Burk) F. H. Chen, Panax ginseng C. A. Meyer and Panax quinquefolius L. are the most representative and valuable herbs world-wide, with a long history of cultivation. As the main bioactive chemical constituents, saponins with different aglycones are the major components in various Panax spp., and their pharmacological activities are mainly reflected in the effects on blood system, cardio- and cerebro-vascular systems, nervous system, metabolism, and immune regulation. Researchers of Kunming Institute of Botany (KIB), Chinese Academy of Sciences (CAS), have put many efforts into conducting the investigations on Panax species. Herein, we reviewed the research progress on Panax spp. in KIB, CAS, over the past few decades, from the aspects of history and origin, phytochemistry and pharmacological activities.

Two New Alkaloids from Fusarium tricinctum SYPF 7082, an Endophyte from the Root of Panax notoginseng.

Panax notoginseng (Araliaceae) is a famous traditional Chinese medicine mainly cultivated in Yunnan and Guangxi provinces of China. Two new alkaloids, rigidiusculamide E (1) and [-(α-oxyisohexanoyl-N-methyl-leucyl)2-] (2), together with two known ones, (-)-oxysporidinone (3) and (-)-4,6'-anhydrooxysporidinone (4) were isolated from the mycelia culture of Fusarium tricinctum SYPF 7082, an endophytic fungus obtained from the healthy root of P. notoginseng. Their structures were determined on the basis of extensive spectroscopic analyses. Compounds 1-4 were tested for their inhibitory effects against NO production on Murine macrophage cell line, and the new compound 2 showed significant inhibitory activity on NO production with the IC50 value of 18.10 ± 0.16 µM.

C-8 N-Ethyl-2-pyrrolidinone-Substituted Flavan-3-ols from the Leaves of Camellia sinensis var. pubilimba.

Camellia sinensis var. pubilimba, one variety of the genus Camellia sect. Thea (Theaceae), has been used for producing green tea mainly by the local people of its growing areas of Guangxi province, China. Forty compounds, including eight C-8 N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (1-8) and their substituted unit N-ethyl-5-hydroxy-2-pyrrolidinone (9), four flavan-3-ol monomers (10-13) and one dimer (14), nine flavonoids (15-23), three hydrolyzable tannins (24-26), two lignans (27-28), 11 simple phenolics (29-39), and caffeine (40), were first isolated and identified from the leaves. Their structures were determined by detailed spectroscopic analysis and comparison with the literature data and authentic samples. Both 1 and 4 were obtained as a mixture of the N-ethyl-2-pyrrolidinone C-5 enantiomers (1a and 1b and 4a and 4b), respectively, while the resolution of another three pairs of enantiomers (2 and 3, 5 and 6, and 7 and 8) was achieved. Among them, 1b is a new compound whose NMR data together with its enantiomer (1a) were reported for the first time, while 2 and 3 are two new natural products. Most of the isolates exhibited significant antioxidant activities, stronger than ascorbic acid and trolox, while parts of the isolates, particularly C-8 N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, showed obvious inhibitory effects on acetylcholinesterase (AChE). The results indicated that C. sinensis var. pubilimba is a valuable plant resource for tea production.

Phyllaciduloids A-D: Four new cleistanthane diterpenoids from Phyllanthus acidus (L.) Skeels.

Four new cleistanthane diterpenoids, phyllaciduloids A-D (1-4), were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels (Phyllanthaceae). Their structures were elucidated on the basis of extensive spectroscopic analysis. Phyllaciduloids B-D (2-4) present in their structures with ether bond between C-7 and C-16, which were rarely reported. All the isolates were evaluated for their cytotoxic activities against five human cancer cell lines.