黄荆酚类成分的研究

目的研究黄荆Vetix negundo Linn.的酚类成分。方法黄荆70%乙醇提取物的乙酸乙酯部位采用硅胶、Sephadex LH-20、ODS柱进行分离纯化,通过波谱数据鉴定所得化合物的结构。结果从中分离得到7个化合物,分别鉴定为木犀草素-4'-O-β-D-吡喃葡萄糖苷(1)、isoorientin 6″-O-caffeate(2)、3,4,5-三咖啡酰奎宁酸(3)、右旋松脂酚酸-4-O-β-D-葡萄糖苷(4)、4-甲氧基-迷迭香酸甲酯(5)、苄基7-O-β-D-葡萄糖苷(6)、丹参素甲酯(7)。结论所有化合物均为首次从该植物中分得,化合物1、3、5~7为首次从牡荆属植物中分得。     

Chemical investigation and anti-inflammatory activity of Vitex negundo seeds.

The CHCl3 extract of the defatted seeds of Vitex negundo exhibited anti-inflammatory activity and yielded four triterpenoids: 3 beta-acetoxyolean-12-en-27-oic acid [1], 2 alpha, 3 alpha-dihydroxyoleana-5,12-dien-28-oic acid [2], 2 beta,3 alpha-diacetoxyoleana-5,12-dien-28-oic acid [3], and 2 alpha,3 beta-diacetoxy-18-hydroxyoleana-5,12-dien-28-oic acid [5]. This is the first report of the isolation of compounds 2, 3, and 5 from a natural source.     

A new triterpenoid glycoside from Vitex negundo

AIM： To investigate the chemical constituents of Fitex negundo. METHOD： Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy. RESULTS： Four compounds were isolated and identified as 2a, 3a, 24-trihydroxyurs-12, 20（30）-dien-28-oic acid-28-O- β-D-glucopyranosyl ester （1）, corosolic acid （2）, vulgarsaponin A （3） and 2a, 3a, 24-trihydroxyurs-12-en-28-oic acid-28-O-β-D- glucopyranosyl ester （4）, respectively. CONCLUSION： Compound I is a new triterpenoid glycoside.     

Antiandrogenic effects of a flavonoid-rich fraction of Vitex negundo seeds: a histological and biochemical study in dogs

The ability of the flavonoid-rich fraction (5,7,3'-trihydroxy, 6,8,4'-trimethoxy flavones) of Vitex negundo seeds to antagonize the androgen action of exogenous testosterone propionate on the male reproductive system was studied in castrated prepubertal and intact adult dog. The flavonoid-rich fraction (F) was administered 10 mg/kg i.p. every other day either alone or in combination with testosterone propionate. The duration of treatment was 30 days in castrates and 60 days in intacts. Treatment with F caused disruption of the latter stages of spermatogenesis. The epididymides were devoid of spermatozoa. Protein, sialic acid and RNA contents of the testes and epididymides were reduced significantly while testicular cholesterol and phosphatase activity in testes and epididymides were elevated. Reduced androgen production was reflected in low levels of sialic acid in testes and epididymides. Castration alone brought about reduction in size and weight of the epididymides whereas castration followed by F treatment caused a reduction in the cellular heights of epididymides. Simultaneous administration of testosterone propionate to F-treated intact adult and castrated prepubertal dogs maintained the viability of spermatozoa, kept epididymal physiology relatively normal and significantly increased the cellular heights of epididymides.     

Phytochemical and Pharmacological Profile of Vitex negundo

The article aims to review all the chemical constituents and pharmacological properties of Vitex negundo L. (Verbenaceae) (VN). VN is an important medicinal plant used as reputed herbal medicine with versatile pharmacological activities in China, India and Japan. A total of 104 referred articles about VN were compiled from major databases and academic publishers, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. As a result, a total of 120 compounds isolated from VN can be divided mainly into four classes: flavonoids, lignans, terpenoids and steroids. The crude extracts and purified compounds of VN exhibited promising bioactivities, including anti‐nociceptive, antiinflammatory, anti‐tumor, anti‐oxidant, insecticidal, antimicrobial, anti‐androgenic, anti‐osteoporotic, anti‐cataract, hepatoprotective and anti‐hyperglycemic activity. All the reported data lead us to conclude that VN has convincing medicinal potential. However, further researches are needed to explore its bioactive constituents, the structure–activity relationship and their molecular mechanisms of action. Copyright © 2015 John Wiley & Sons, Ltd.     

牡荆叶化学成分研究

目的：研究牡荆叶Vitex negundo L. var. cannabifolia的化学成分。方法：采用硅胶、葡聚糖凝胶Sephadex LH?20、十八烷基硅烷键合硅胶（ODS）和半制备HPLC等柱色谱技术,对牡荆叶的化学成分进行分离纯化,结合其理化性质及MS、NMR等光谱数据鉴定化合物的结构。结果：从牡荆叶95%乙醇提取物的醋酸乙酯萃取部位分离得到11个化合物,分别鉴定为芹菜素（1）、5,4′-二羟基-3,6,7-三甲氧基黄酮（2）、猫眼草酚（3）、槲皮素（4）、1,4-二羟基（3R,5R）-二咖啡酰氧基环己甲酸甲酯（5）、灰毡毛忍冬素F（6）、椒二醇（7）、caryolandiol（8）、β-谷甾醇（9）、对羟基苯甲酸（10）和β-胡萝卜苷（11）。结论：化合物5?8为首次从牡荆属植物中分离得到,化合物1、4为首次从牡荆叶中分离得到。     

黄荆根提取物抗炎镇痛作用研究

目的：观察黄荆根乙酸乙酯提取物的抗炎、镇痛作用。方法：采用二甲苯诱导小鼠耳廓肿胀和角叉菜胶诱导大鼠足肿胀建立炎症模型观察黄荆根乙酸乙酯提取物的抗炎作用;采用扭体法和热板法观察黄荆根乙酸乙酯提取物的镇痛作用。结果：黄荆根提取物各剂量（16g·kg^-1、8g·kg^-14g·kg^-1）均能对二甲苯诱导的小鼠耳肿胀产生抑制作用（P〈0．05）;也能明显抑制角叉菜胶诱导的大鼠足肿胀（P〈0．05）。对热刺激和醋酸刺激引起的小鼠疼痛,黄荆根提取物高、中剂量（16g·kg^-1、8g·kg^-1）具有显著的镇痛作用（P〈0．05）。结论：黄荆根乙酸乙酯提取物具有抗炎镇痛作用。     

Cytotoxic flavone analogues of vitexicarpin,a constituent of the leaves of Vitex negundo

Bioassay-guided fractionation of the chloroform-soluble extract of the leaves of Vitex negundo led to the isolation of the known flavone vitexicarpin (1), which exhibited broad cytotoxicity in a human cancer cell line panel. In an attempt to increase the cytotoxic potency of 1, a series of acylation reactions was performed on this compound to obtain its methylated (2), acetylated (3), and six new acylated (4-9) derivatives. Compound 9, the previously unreported 5,3'-dihexanoyloxy-3,6,7,4'-tetramethoxyflavone, showed comparative cytotoxic potency to compound 1 and was selected for further evaluation. However, this compound was found to be inactive when evaluated in the in vivo hollow fiber assay with Lu1, KB, and LNCaP cells at the highest dose (40 mg/kg/body weight) tested, and in the in vivo P-388 leukemia model (135 mg/kg), using the ip administration route.     

Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo

This study confirmed the oral anti-inflammatory, analgesic and antihistamine properties of mature fresh leaves (MFL) of Vitex negundo L. (Verbenaceae) claimed in the Ayurveda medicine by orally treating a water extract of the leaves to rats. The early phase (2h) of carrageenan-induced rat paw oedema was significantly (P<0.01) suppressed in an inversely does-dependent (r(2)=1, P<0.01) manner by MFL. The EC(50) was 2g/kg of MFL. In the formaldehyde-induced rat paw oedema test, the 2.5 and 5g/kg leaves significantly (P<0.05) suppressed the inflammation on days 4-6 of the test. In the hot plate test, 2.5 and 5g/kg of MFL showed a significant (P<0.05) and directly dose-dependent analgesic activity at 1h of treatment while the activity was absent in the tail flick test in rats. The EC(50) for the analgesic activity was 4.1g/kg. In the formalin test, 1.25, 2.5 and 5g/kg of MFL significantly (P<0.05) suppressed the pain in both the phases of the test like aspirin. The leaves showed an inversely dose-dependent in vivo antihistamine and in vitro prostaglandin (PG) synthesis inhibition, membrane stabilising and antioxidant activities. Naloxone did not abolish the analgesic activity in the hot plate test. A 5g/kg of MFL did not impair muscle strength and co-ordination and did not induce sedation. The treatment of 5g/kg of MFL did not show signs of acute toxicity or stress. Fourteen-day oral treatment of 5g/kg of MFL significantly increased the serum activity of AST. Flowering of the tree did not abolish the analgesic and anti-inflammatory activities of the leaves. These observations revealed that the fresh leaves of Vitex negundo have anti-inflammatory and pain suppressing activities possibly mediated via PG synthesis inhibition, antihistamine, membrane stabilising and antioxidant activities. The antihistamine activity can produce the anti-itching effect claimed in Ayurveda medicine.     

Total lignans from Vitex negundo seeds attenuate osteoarthritis and their main component vitedoin A alleviates osteoclast differentiation by suppressing ERK/NFATc1 signaling

The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T_1/2) was 2.82 h and 1.33 h, and the bioavailability was 15.34%–21.89% and 16.29%–22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.     

Isolation,characterization and biological activity of betulinic acid and ursolic acid from Vitex negundo L

Two pentacyclic triterpenoids, betulinic acid (3beta-hydroxylup-20-(29)-en-28-oic acid) (3), and ursolic acid (2beta-hydroxyurs-12-en-28-oic acid) (4), were isolated for the first time from leaves of Vitex negundo L. along with three other compounds; an aliphatic alcohol n-hentriacontanol (1), beta-sitosterol (2) and p-hydroxybenzoic acid (5). Their antifeedant activity against the larvae of an agricultural pest, the castor semilooper (Achoea janata), in a no-choice laboratory assay and their antibacterial activity against Bacillus subtilis and Escherichia coli, by the paper disc method, were tested. Ursolic acid (4) showed more effective antifeedant activity than the betulinic acid (3). However, both these compounds have shown a very mild antibacterial activity. The other three compounds; n-hentriacontanol (1), beta-sitosterol (2) and p-hydroxybenzoic acid (5) have shown a little antifeedant activity against the larvae and did not show any antibacterial activity.     

黄荆子乙酸乙酯提取物对人乳腺癌MCF-7细胞Mcl-1、Bcl-2、Bax蛋白的影响

目的研究黄荆子乙酸乙酯提取物(EVn-50)对人乳腺癌MCF-7细胞Mcl-1、Bcl-2、Bax蛋白的作用。方法应用Wersten Bloting分析EVn-50对人乳腺癌MCF-7细胞Mcl-1、Bax和Bcl-2蛋白表达的影响。结果 Evn-50使Mcl-1及Bcl-2值下调,Bax值上调,促进细胞凋亡。且EVn-50中浓度组相对灰度面积比值与低浓度组比较有显著性差异(P均0.05),EVn-50组48 h相对灰度面积比值与24 h比较有显著性差异(P均0.05)。结论 EVn-50具有诱导人乳腺癌MCF-7细胞凋亡的作用,最佳浓度为3.0 mg/L,最佳作用时间为48 h。     

Reproduction in male rats is vulnerable to treatment with the flavonoid-rich seed extracts of Vitex negundo

A partially purified flavonoid-rich extract was prepared from the seed of Vitex negundo. The effect of this extract on the reproductive system of male rats was investigated at four different concentrations. All the major accessory sex organs shed weight when the preparation was administered at doses of >or=15 mg/rat/day after 15 days of treatment. The drop in weight was also reflected in disturbed tissue biochemistry. Secretory products such as citric acid in the prostate, fructose in seminal vesicles and epididymal alpha-glucosidase activity, indices of accessory sex organ function in males, diminished. Microscopic examination of the sperm derived from the cauda epididymides of treated animals showed only a marginal change in vitality. However, sperm numbers dwindled and slackness in their motility was observed, factors that may impede fertility. Toxicity testing in blood did not point to distress in any of the vital organs. Taken together, it is inferred that the seed extracts of V. negundo interfere with male reproductive function without producing adverse toxicity in other vital organs.     

Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis) root extracts

The methanolic root extracts of Vitex negundo Linn. and Emblica officinalis Gaertn. were explored for the first time for antisnake venom activity. The plant (V. negundo and E. officinalis) extracts significantly antagonized the Vipera russellii and Naja kaouthia venom induced lethal activity both in in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory activity was significantly neutralized by both plant extracts. No precipitating bands were observed between the plant extract and snake venom. The above observations confirmed that the plant extracts possess potent snake venom neutralizing capacity and need further investigation.     

Identification of chrysoplenetin from Vitex negundo as a potential cytotoxic agent against PANC-1 and a panel of 39 human cancer cell lines (JFCR-39)

Human pancreatic cancer is known to be the most deadly disease with the lowest 5‐year survival rate and is resistant to well known conventional chemotherapeutic drugs in clinical use. Screening of medicinal plants from Myanmar utilizing antiausterity strategy led to the identification of Vitex negundo as one of the medicinal plants having potent preferential cytotoxic activity against PANC‐1 human pancreatic cancer cells. Bioactivity‐guided phytochemical investigation led to the isolation of chrysoplenetin (1) and chrysosplenol D (2) as the active constituents with a PC₅₀ value of 3.4 μg/mL and 4.6 μg/mL, respectively, against PANC‐1 cells. Both these compounds induced apoptosis‐like morphological changes in PANC‐1 cells. Chrysoplenetin was further tested against a panel of 39 human cancer cell lines (JFCR‐39) at the Japanese Foundation for Cancer Research, and 25 cell lines belonging to lung, breast, CNS, colon, melanoma, ovarian, prostate cancer and stomach cancer cell lines were found to be highly sensitive to chrysoplenetin at a submicromolar range. In the JFCR‐39 panel, lung NCI‐H522, ovarian OVCAR‐3 and prostate PC‐3 cells were found to be most sensitive with GI₅₀ of 0.12, 0.18 and 0.17 μm , respectively. The COMPARE analysis suggested that the molecular mode of action of chrysoplenetin was unique compared with the existing anticancer drugs. Copyright © 2011 John Wiley & Sons, Ltd.     

Bisnorditerpene, norditerpene, and lipo-alkaloids from Aconitum toxicum

From the roots of Aconitum toxicum, acotoxicine (1), a new bisnorditerpene alkaloid, was isolated together with the structurally related delavaconitine, delavaconine, dolaconine, aconosine, and the norditerpene alkaloid neolinine. The structure of compound 1 was elucidated by spectroscopic data interpretation. Further, eight lipo-alkaloids (2-9) were detected in the plant material by LC-APCI-MSn analysis. This is the first report of a C18 bisnorditerpene alkaloid and lipo-alkaloids from A. toxicum.     

华中五脂素--华中五味子种子中得到的新木脂素

目的：对华中五味子种子的化学成分进行研究，方法：运用各种色谱技术对其化学成分进行分离，波谱方法鉴定化学结构。结果：从华中五味子种子95％乙醇提取物的乙醚萃取物中分离得到华中五脂素(1)，安五脂素(2)，五味子酯甲(3)，五味子甲素(4)，顺酯酰戈米辛O(5)，6-O-苯甲酰戈米辛O(6)和五味子酮(7)7个木脂素类化合物．结论：化合物1为新的二芳基丁烷类木脂素，命名为华中五脂素；化合物6为首次从该植物中分离得到。     

Lignan derivatives from Krameria lappacea roots inhibit acute inflammation in vivo and pro-inflammatory mediators in vitro

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID?? 77 μg/cm2) as well compounds 1-11 (ID?? 0.31-0.60 μmol/cm2) exhibited topical antiedematous properties comparable to those of indomethacin (ID?? 0.29 μmol/cm2) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E? synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.     

驱虫斑鸠菊中咖啡酰基奎宁酸类化学成分

目的:采用大孔吸附树脂、Sephadex LH-20以及制备HPLC等色谱方法对驱虫斑鸠菊Vernonia anthelmintica成熟种子进行分离纯化,分离得到6个化合物。通过1H,13C-NMR及MS等波谱技术鉴定化合物的结构,分别为咖啡酸(1),3-O-咖啡酰基奎宁酸(2),4-O-咖啡酰基奎宁酸(3),5-O-咖啡酰基奎宁酸(4),表-3,4-O-双咖啡酰基奎宁酸(5),3,4-O-双咖啡酰基奎宁酸(6)。其中,化合物1～6均为首次从该植物中分离得到,其中3～5为首次从该属植物中分离得到。     

Diterpenes from the fruits of Vitex rotundifolia

Eight new labdane-type diterpenes (1-8) were isolated from the fruit of Vitex rotundifolia along with two known abietane-type diterpenoids (9, 10), and their structures were characterized on the basis of spectroscopic data and X-ray crystallographic analysis. Among them, the abietane-type diterpenoid ferruginol (9) exhibited a stronger antioxidative activity than the standard antioxidant, 3-tert-butyl-4-hydroxyanisole (BHA), using a ferric thiocyanate method.