Synthesis of oleanolic acid saponins mimicking components of Chinese folk medicine Di Wu

3,28-Di-O-rhamnosylated oleanolic acid saponins, mimicking components of Chinese folk medicine Di Wu, have been designed and synthesized. One-pot glycosylation and ‘inverse procedure’ technologies have been applied thus significantly simplifying the preparation of desired saponins. The cytotoxic activity of compounds 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl]oleanolic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester (3), 3-O-[α-l-rhamnopyranosyl]oleanolic acid 28-O-[α-l-rhamnopyranosyl- (1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester (4), 3-O-[α-l-rhamnopyranosyl]oleanolic acid 28-O-[α-l-rhamnopyranosyl] ester (5), and 3-O-[α-l-rhamnopyranosyl]oleanolic acid 28-O-[6-O-(α-l-rhamnopyranosyl)hexyl] ester (6) was preliminarily evaluated against HL-60 human promyelocytic leukemia cells. The natural saponin 3 and designed saponin 4 exhibited comparable moderate cytotoxic activity under our testing conditions.     

Synthesis of stryphnoside A, a triterpene saponin isolated from the pericarps of Stryphnodendron fissuratum

Stryphnoside A, α-l-rhamnopyranosyl 3β-O-[α-l-arabinopyranosyl-(1→4)-β-d-xylopyranosyl-(1→2)-β-d-glucopyranosyl]-2α-hydroxyolean-12-en-28-oate, has been synthesized in 11 steps in 15% overall yield starting from the naturally abundant oleanolic acid. Condensation of a partially protected glucopyranosyl donor and 2α,3β-dihydroxyolean-12-en-28-oic acid derivative using inverse glycosylation procedure has significantly simplified the target saponin synthesis. Stryphnoside A exhibited weak cytotoxic activities against tumor cells HeLa, A549, and HepG2 with IC₅₀ at mM level.     

Synthesis of oligosaccharide derivatives related to those from sanqi, a Chinese herbal medicine from Panax notoginseng

Oligosaccharide derivatives from sanqi, a Chinese herbal medicine derived from Panax notoginseng, methyl beta-D-galactopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->6)]-alpha-D-galactopyranoside, diosgenyl beta-D-galactopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->6)]-alpha-D-galactopyranoside, and methyl beta-D-galactopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->6)]-alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->6)]-alpha-D-galactopyranoside, were synthesized under standard glycosylation conditions. An unexpected alpha-(1-->4) linkage was formed predominantly in the presence of neighboring participation group during regioselective synthesis of hexasaccharide via 3+3 strategy.     

Five heavy metals accumulation and health risk in a traditional Chinese medicine Cortex Moutan collected from different sites in China

This study assessed the concentrations of five heavy metals Pb, Cd, Cr, Cu and Zn in both soil and a traditional Chinese medicine Cortex Moutan collected from 6 typical sites, growing this medicine, in China. The potential health risks associated with those heavy metals were also assessed. It is shown that Cd content in soils from five of the six sites was higher than the environmental Quality Standard for Soils of China (EQSS). The cortex from a copper tailings area in Tongling (marked as TLC) accumulated much higher amounts of heavy metals than the other sites. Calculated pollution index implied that the herbs in TLC were mildly contaminated by Pb, Cd, and Cu. Hazard quotient (HQ) indicated the intake of Pb, Cd, Cr, Cu, and Zn was safe by cortex consumption, but noncarcinogenic and carcinogenic risks of all metals in Cortex Moutan in hillside near the copper tailings (marked as TLB) and TLC were higher. The results suggested more attention should be paid to the planting area near the mining tailing, and in order to ensure the quality of the herbal medicines, the regions where this herb is grown should be at distance from the mining tailing area.     

Structure of acacigenin-B,a novel triterpene ester isolated from Acacia concinna

The structure of acacigenin-B, a novel ester genin from the pods of Acacia concinna was established from its PMR and ¹³ C NMR spectra. It was identified as the 21-hydroxy ester of acacic acid; the esterifying acid was a hitherto unknown monoterpene acid of tetrahydrofuranoid structure. This appears to be the first report of a higher terpenoid forming an ester with a monoterpene acid     

从野生动物资源角度探讨中医药业的可持续发展

野生动物资源是中医药业的主要物质基础之一。目前,生物多样性急剧下降,物种灭绝速度加快,许多药用野生动物濒临灭绝,严重阻碍了中医药业的可持续发展。在许多野生动物野外种群难以恢复或恢复速度很慢、寻找中医药动物原材料的替代品短期内难以实现的情况下,开辟中医药原材料来源渠道是促进中医药业可持续发展的主要措施之一。在正确认识野生动物保护与利用的关系的前提下,妥善、高效利用人工驯养繁殖、库存野生动物产品,遵循经济效益、社会效益、生态效益的原则,优先保障重点领域、重点产业的需要,并发挥市场配置资源的积极作用,充分实现有限资源的合理配置,以促进野生动物资源保护与中医药业可持续发展的良性循环。     

禽源致病性大肠埃希菌的耐药性与中草药有效成分的抑菌活性测定

以28株合肥地区禽源致病性大肠埃希菌为实验材料,采用K-B纸片琼脂扩散法检测禽源致病性大肠埃希菌的耐药情况。同时采用平板打孔法测定盐酸小檗碱、绿原酸、靛玉红和丹参酮ⅡA 4种中草药有效成分的抑菌活性。结果表明,28株禽源致病性大肠埃希菌对17种抗菌药物均呈现不同程度的耐药性,对β-内酰胺类、氨基糖苷类、四环素类和喹诺酮类抗菌药物的耐药率分别介于0%～92.86%、14.29%～50.00%、78.57%～100%和57.14%～71.43%。中草药有效成分盐酸小檗碱和丹参酮ⅡA对大肠埃希菌具有较好的抑制活性,抑菌率分别为92.86%（26/28）和89.29%（25/28）。     

抑郁症发病机制及中药治疗研究进展

抑郁症是一种常见的精神疾病,发病率高,严重威胁着人类的健康,但其病因、发病机制尚不清楚,由于合成抗抑郁药大多存在抗抑郁谱窄、不良反应大、药价高和易复发等缺陷,近年来随着人们对抑郁症发病机制的研究,人们逐渐把目光投向传统的中医药,以期从中寻找出多靶点、低毒的抗抑郁药。现对近年来抑郁症的病因、病机、及中药治疗的研究情况做一综述     

Propionibacterium acnes related anti-inflammation and skin hydration activities of madecassoside,a pentacyclic triterpene saponin from Centella asiatica

Madecassoside is a major pentacyclic triterpene saponin from Centella asiatica with multiple pharmaceutical activities. In this study, we focused on its Propionibacterium acnes related anti-inflammation and skin hydration activities, both of which play important roles in skin homeostasis and barrier function. Madecassoside significantly inhibited the pro-inflammatory cytokine IL-1β, TLR2 and nuclear translocation of NF-κB in P. acnes stimulated THP-1 human monocytic cells. In addition, madecasssoside exhibited significant effects on enhancement of skin hydration through increasing the key moisturizing contributors of aquaporin-3, loricrin and involucrin in HaCaT keratinocytes as well as hyaluronan (HA) secretion in human dermal fibroblasts. The upregulation of HA synthases (HAS1, HAS2, HAS3) and inhibition to ROS formation accounted for the increment of HA content. Together, the in vitro study implied the potential medical and cosmetic application of madecassoside in skin protection.     

试论肠菌与中草药联合和发酵防治疾病

【摘 要】 本文阐述了肠道原始固有菌群（肠菌）与天然药用植物（中草药）联合应用和用肠菌发酵中草药的可行性及应用前景。     

Molecular profile of the unique species of traditional Chinese medicine,Chinese seahorse (Hippocampus kuda Bleeker)

A cDNA library of male Chinese seahorse (Hippocampus kuda Bleeker) was constructed to investigate the molecular profile of seahorse as one of the most famous traditional Chinese medicine materials, and to reveal immunological and physiological mechanisms of seahorse as one of the most primitive vertebrates at molecular level. A total of 3372 expressed sequence tags (ESTs) consisting of 1911 unique genes (345 clusters and 1566 singletons) were examined in the present study. Identification of the genes related to immune system, paternal brooding and physiological regulation provides not only valuable insights into the molecular mechanism of immune system in teleost fish but also plausible explanations for pharmacological activities of Chinese seahorse. Furthermore, the occurrence of high prevalent C-type lectins suggested that a lectin-complement pathway might exert a more dominant function in the innate immune system of teleost than mammal. Carbohydrate recognition domain (CRD) without a collagen-like region in the lectins of seahorse was likely an ancient characteristic of lectins similar to invertebrates.     

Synthesis of (R)-(+)-hippospongic acid A, a triterpene isolated from the marine sponge, Hippospongia sp.

Hippospongic acid A (1) is a triterpene metabolite of the marine sponge, Hippospongia sp., with inhibitory activity against the gastrulation of starfish embryos. (R)-(+)-1 was synthesized by employing enzymatic kinetic resolution as the key step.     

Synthesis and antifungal activity of ASP9726, a novel echinocandin with potent Aspergillus hyphal growth inhibition

The synthesis and antifungal activity of ASP9726, a novel echinocandin with potent Aspergillus hyphal growth inhibition and significantly improved MIC against Candida parapsilosis and echinocandin resistant-Candida is described.     

No effect of a traditional Chinese medicine, Hochu-ekki-to, on antibody titer after influenza vaccination in man: A randomized, placebo-controlled, double-blind trial

BACKGROUND: It was shown that a traditional Chinese medicine, Hochu-ekki-to (HET), had adjuvant effects in influenza vaccination in an animal experiment. This, however, could not be assessed in a clinical study. METHODS: Thirty-two healthy subjects were randomly assigned to two groups (control and HET groups) in a double-blind manner. HET subjects (n=17) took 7.5 g of HET/day for two weeks; control subjects took the same amount of indistinguishable placebo. Then subjects were vaccinated against influenza (H1N1, H3N2 and B/Shandong). Hemagglutinin titers and natural killer (NK) activity were measured at weeks 0, 1, 2, 4, and 12. RESULTS: Antiinfluenza titers against the three viruses were increased continuously for the first two weeks and leveled off. However, there were no significant differences in any titers between the two groups. NK activity peaked at week 2 without any inter-group differences. CONCLUSION: We could not find any adjuvant effects of HET in this experimental condition.     

四川宜宾七种中药提取物体外抗菌活性研究

用肉汤二倍稀释法和琼脂平板培养计数法,研究四川宜宾七种中药的提取物对大肠杆菌、沙门氏菌和巴氏杆菌的体外抑制作用.结果表明：黄柏提取物的抗菌活性最强,最小抑菌浓度(Minimum inhibitory concentration,MIC)为15．6~125 mg·mL-1,最小杀菌浓度(Minimum bactericidal concentration,MBC)为31．25~250 mg·mL-1;栀子提取物抗菌活性次之,MIC 为62．5~125 mg·mL-1,MBC 为125~＞250 mg·mL-1;佛手提取物有较稳定的抗菌活性,MIC均为125 mg·mL-1,MBC为125 mg·mL-1和250 mg·mL-1;姜黄、杜仲、何首乌、细毡毛忍冬的提取物抗菌活性相对较差,大部分 MIC≥250 mg·mL-1.说明四川宜宾的黄柏和栀子的提取物抗菌活性较强,佛手提取物抗菌活性较稳定,有进一步研究的价值.     

Synthesis and anticancer activity of focused compound libraries from the natural product lead,oroidin

Oroidin (1), (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dibromo-1H-pyrrole-2-carboxamide, is a pyrrole alkaloid isolated from the marine sponge Agelas oroides. Routine screening in a panel of twelve cancer cell lines revealed 1 to be poorly cytotoxic with the 50% growth inhibition concentration (GI₅₀) of 42 μM in MCF-7 (breast) cells and 24 μM in A2780 (ovarian) cells and >50 μM in all other cell lines tested. The development of eight focused libraries comprising thirty compounds total identified N-(biphenyl-4-ylmethyl)-1H-pyrrole-2-carboxamide (4l), N-benzyl-4,5-dibromo-1H-pyrrole-2-carboxamide (5a) and N-(biphenyl-4-ylmethyl)-4,5-dibromo-1H-pyrrole-2-carboxamide (5l) as potent inhibitors of cell growth in our panel of cell lines. Of these compounds GI₅₀ values of <5 μM were observed with 4l against HT29 (colon) and SW480 (colon); 5a against HT29; and 5l against HT29, SW480, MCF-7, A431 (skin), Du145 (prostate), BE2-C (neuroblastoma) and MIA (pancreas) cell lines. As a cancer class, colon cancer appears to be more sensitive to the oroidin series of compounds, with analogue 5l being the most active.     

中国人Ⅱ型MPS家系IDS基因的一种新突变的鉴定

为了研究粘多糖贮积症Ⅱ型(MPSⅡ)患者发病的分子遗传学机制, 以便为今后的产前基因诊断等创造必要的前提条件, 文章先采用尿糖胺聚糖(GAGs)定性检测法对疑似MPSⅡ的先证者进行初诊, 然后采用PCR、PCR 产物直接测序法对先证者及其家系成员进行突变检测。在检出IDS基因c.876del2新突变后, 对随机采集的120例正常对照和其他非II型MPS患者包括MPSⅠ, Ⅳ, Ⅵ三型的病人共15例的IDS基因exon 6进行序列分析, 同时采用不同物种突变点序列的保守性分析法, 以及直接测定患儿及其家庭相关成员IDS酶活性的方法对该新突变进行致病性分析。结果显示: 先证者尿检呈强阳性(GAGs +++); 其IDS基因exon 6编码区内存在c.876-877 del TC新缺失突变, 为半合子突变, 而其母、其姐为杂合突变; 正常对照和其他非II型MPS患者的IDS基因exon 6的检测结果均未发现该突变; 不同物种氨基酸序列的同源性比对显示: c.876-877 del TC突变所在的位置即p.292-293的苯丙氨酸(F)谷氨酰胺(Q)高度保守; 酶活性测定的结果显示: 先证者的IDS酶活性仅为2.3 nmol/4 h/mL, 大大低于正常值, 而其父的为641.9 nmol/4 h/mL, 其母的血浆酶活性为95.8 nmol/ 4h/mL, 其姐的为103.2 nmol/4 h/mL。说明所发现的c.876-877 del TC缺失移码突变是一种新的病理性突变, 是该MPSⅡ患儿发病的根本内因。     

Highly selective antibacterial activity of novel alkyl quinolone alkaloids from a Chinese herbal medicine, Gosyuyu (Wu-Chu-Yu), against Helicobacter pylori in vitro

To elucidate the antibacterial activity of Gosyuyu, the crude extract from the fruit of Evodia rutaecarpa, a Chinese herbal medicine, has been fractionated chromatographically, and each fraction was assayed for antibacterial activity against Helicobacterpylori (H. pylori) in vitro. As the result, a single spot having marked antibacterial activity against H. pylori was obtained and the chemical structure was analyzed. The isolated compound was revealed to be a novel alkyl quinolone alkaloid based on the solubility, IR spectra, NMR analysis and mass spectrometric data after purification by TLC of silica. We compared the antimicrobial activity of this compound with that of other antimicrobial agents and examined susceptibility of various intestinal pathogens. As the result, the new quinolone compounds obtained from Gosyuyu extracts were found to be a mixture of two quinolone alkaloids, 1-methyl-2-[(Z)-8-tridecenyl]-4-(1H)-quinolone and 1-methyl-2-[(Z)-7-tridecenyl]-4-(1H)-quinolone (MW: 339), reported previously. The minimum inhibitory concentration (MIC) of these compounds against reference strains and clinically isolated H. pylori strains were less than 0.05 microg/ml, which was similar to the MIC of amoxicillin and clarithromycin that are used worldwide for the eradication of H. pylori, clinically. Furthermore, it was noted that the antimicrobial activity of these compounds was highly selective against H. pylori and almost non-active against other intestinal pathogens. The above results showed that these alkyl methyl quinolone (AM quinolones) alkaloids were useful for the eradication of H. pylori without affecting other intestinal flora.     

Cytotoxic activity of hirsutanone,a diarylheptanoid isolated from Alnus glutinosa leaves

BackgroundThe low efficacy of cancer therapy for the treatment of patients with advanced disease makes the development of new anticancer agents necessary. Because natural products are a significant source of anticancer drugs, it is important to explore cytotoxic activity of novel compounds from natural origin.PurposeThe aim of this work is to evaluate the cytotoxic capacity of hirsutanone, a diarylheptanoid isolated from Alnus glutinosa leaves. Hirsutanone cytotoxic way of action was also studied.Material and methodsThe cytotoxic ability of Alnus glutinosa leaves ethyl acetate extract was studied over HeLa and PC-3 cell lines, with the MTT colorimetric assay. Hirsutanone was isolated from this extract using chromatographic methods, and its structure elucidated by spectroscopic analysis. HT-29 cell viability after hirsutanone treatment was determined using SRB assay. In order to understand hirsutanone way of action, cytotoxicity was evaluated adding the diarylheptanoid and antioxidants. DNA topoisomerase II (topo II) poison activity, was also evaluated using purified topo II and a supercoiled form of DNA that bears specific topo II recognition and binding region; topo II poisons stabilize normally transient DNA-topo II cleavage complexes, and lead an increased yield of linear form as a consequence of a lack of double-strand breaks rejoining.ResultsThe diarylheptanoid hirsutanone was isolated from Alnus glutinosa (L.) Gaertn. (Betulaceae) leaves extract that showed cytotoxic activity against PC-3 and HeLa cell lines. Hirsutanone showed cytotoxic activity against HT-29 human colon carcinoma cells. Pre-treatment with the antioxidants NAC (N-acetylcysteine) and MnTMPyP (Mn(III)tetrakis-(1-methyl-4-pyridyl)porthyrin) reduced this activity, suggesting that reactive oxygen species (ROS) participate in hirsutanone-induced cancer cell death. Using human topo II and a DNA supercoiled form, hirsutanone was found to stabilize topo II-DNA cleavage complexes, acting as a topo II poison.ConclusionOur data suggest that, like curcumin, an induction of oxidative stress and topo II-mediated DNA damage may play a role in hirsutanone-induced cancer cell death. Since both compounds share similar structure and cytotoxic profile, and curcumin is in clinical trials for the treatment of cancer, our results warrant further studies to evaluate the anticancer potential of hirsutanone.