Ex vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats.

Picroliv, the active constituent isolated from the plant Picrorhiza kurroa, was evaluated as a hepatoprotective agent against ethanol-induced hepatic injury in rats. Alcohol feeding (3.75 g/kg x45 days) produced 20-114% alteration in selected serum (AST, ALT and ALP) and liver markers (lipid, glycogen and protein). Further, it reduced the viability (44-48%) of isolated hepatocytes (ex vivo) as assessed by Trypan blue exclusion and rate of oxygen uptake. Its effect was also seen on specific alcohol-metabolizing enzymes (aldehyde dehydrogenase, 41%; acetaldehyde dehydrogenase, 52%) in rat hepatocytes. The levels of these enzymes were found to be reduced in the cells following alcohol intoxication. Ethyl alcohol also produced cholestasis (41-53%), as indicated by reduction in bile volume, bile salts and bile acids. Picroliv treatment (3-12 mg/kg p.o. x45 days) restored the altered parameters in a dose-dependent manner (36-100%).     

Prevention of paracetamol-induced hepatic damage in rats by picroliv,the standardized active fraction from Picrorhiza kurroa

Single oral administration of paracetamol (2 g/kg body wt) to rats caused significant changes in the activities of γ-glutamyl transpeptidase, 5′-nucleotidase, succinate dehydrogenase, glucose-6-phosphatase and cytochrome P₄₅₀ and contents of glycogen and cholesterol in liver after 24 and 48 h. Total lipids and lipid peroxides in liver increased both at 24 and 48 h while protein content of liver decreased after 48 h. Levels of transaminases, alkaline phosphatase and bilirubin in serum also increased. The magnitude of these changes was more after 48 h of paracetamol administration. Picroliv, the iridoid glycoside fraction of Picrorhiza kurroa, when given orally to rats (6 and 12 mg/kg body wt for 7 days) caused significant reversal of the paracetamol-induced biochemical changes. The degree of protection at the two doses of picroliv was almost similar.     

Immunodulatory compounds from Picrorhiza kurroa: isolation and characterization of two anti-complementary polymeric fractions from an aqueous root extract

Two aqueous root extracts of Picrorhiza kurroa, one prepared by extraction at 4 degrees C and the other by refluxing, were purified using the guidance of modulation of classical (CP) and alternative (AP) pathway complement activity. By means of methanol extraction and gel filtration chromatography, two polymeric fractions were isolated from the cold water extract. A methanol-soluble polymeric fraction (CS1) was highly active in inhibiting CP complement activity exclusively, whereas a methanol-insoluble polymeric fraction (CI1) exhibited an inhibitory effect on both CP and AP complement activity. Preliminary chemical analysis of the anti-complementary fractions revealed the presence of structures of carbohydrate and of peptide nature in CS1 and CI1. The modulation of CP complement activity by CS1 was studied in more detail. Its inhibitory effect was proven to be based on complement consumption rather than on chelation of Ca2+ and/or Mg2+ or on stabilization of the target cells in the complement-assay. The purification of the aqueous extract prepared by refluxing, resulted in the isolation of a polymeric fraction with the same qualities as CS1. However, a fraction with properties similar to CI1 could not be isolated from this extract.     

Picrorhiza kurroa Inhibits Experimental Arthritis Through Inhibition of Pro‐inflammatory Cytokines,Angiogenesis and MMPs

The present study investigates the anti‐arthritic activity of Picrorhiza kurroa (PK), on formaldehyde and adjuvant‐induced arthritis (AIA) in rat. Administration of Picrorhiza kurroa rhizome extract (PKRE) significantly inhibited joint inflammation in both animal models. In AIA‐induced arthritic rat, treatment with PKRE considerably decreased synovial expression of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor receptor‐1 (TNF‐R1) and vascular endothelial growth factor as compared with control. The anti‐arthritic activity was found to be well substantiated with significant suppression of oxidative and inflammatory markers as there was decreased malonaldehyde, Nitric oxide, tumor necrosis factor alpha levels accompanied with increased glutathione and superoxide dismutase, catalase activities. Additionally, PKRE significantly inhibited the expression of degrading enzymes, matrix metalloproteinases‐3 and matrix metalloproteinases‐9 in AIA‐induced arthritic rat. Histopathology of paw tissue displayed decreased inflammatory cell infiltration as compared with control. Taken together, these results demonstrated the anti‐arthritic activity of PKRE against experimental arthritis, and the underlying mechanism behind this efficacy might be mediated by inhibition of inflammatory mediators and angiogenesis, improvement of the synovium redox status and decreased expression of matrix metalloproteinases. Copyright © 2015 John Wiley & Sons, Ltd.     

Gastrointestinal effects of Mebarid,an ayurvedic formulation,in experimental animals

Mebarid, an ayurvedic formulation, was tested for its anti-diarrhoeal, anti-ulcer and anti-motility activities in animals. Mebarid was investigated at four dose levels of 125, 250, 500 mg/kg BW and 1g/kg BW The methods of castor oil-induced diarrhoea and pylorus-ligation-induced ulcers in rats were used to evaluate the anti-diarrhoeal and anti-ulcer activity, respectively, while charcoal meal test in mice was the method used for testing its anti-motility effect. Mebarid was found to have significant activity in all the three models. Thus, it can be concluded that Mebarid possesses anti-diarrhoeal, anti-motility and anti-ulcer activities and can prove beneficial in the treatment of above gastrointestinal disorders.     

Non-narcotic orally effective,centrally acting analgesic from an ayurvedic drug

Embelin, a p-quinone, is derived from Embelia ribes Burm. The analgesic effect of potassium embelate has been studied in rats and mice. The test drug was found to be effective by oral, i.m. and i.c.v. routes and the results compared well with morphine. Although potassium embelate acts centrally to produce analgesia, its effect is not antagonized by naloxone indicating a different central site of action. There is no precipitation of abstinence syndrome as observed with morphine. Peripheral site of action of the drug is ruled out as it lacks any demonstrable anti-inflammatory action. It can be concluded that high oral efficacy and non-narcotic properties of the test drug make it more acceptable than morphine. In addition, lack of any adverse effects, high therapeutic index and absence of abstinence syndrome confers a long term safety on potassium embelate for use as an analgesic.     

Occurrence of resveratrol and pterostilbene in age-old darakchasava, an ayurvedic medicine from India

'Darakchasava' is a well known Indian herbal preparation of which the main ingredient is Vitis vinifera L. This 'ayurvedic' medicine is prescribed as a cardiotonic and also given for other disorders. HPLC analysis of this age old formulation revealed the presence of polyphenols like resveratrol and pterostilbene. These phenolic compounds are now known as antioxidants, cancer chemopreventive agents, and also known to reduce mortality from coronary heart disease by increasing high density lipoproteins like cholesterol and inhibiting platelet aggregation (Soleas, J.S., Diamandis, E.P., Goldberg, D.M., 1997. Resveratrol: a molecule whose time has come? and gone? Clin. Biochem. 30 (2), 91-113). The study of darakchasava becomes interesting in the light of these findings. A brief introduction of this medicinal preparation, its formulation, its analysis by HPLC, and some of its properties are discussed in this article.     

Terminalia arjuna,an ayurvedic cardiotonic,increases contractile force of rat isolated atria

The direct effects of aqueous, ethanolic, chloroform and petroleum ether extracts of Terminalia arjuna (family: Combretaceae) bark, an ayurvedic remedy for cardiovascular disorders, were studied on isolated atria of rats. The aqueous extract produced a substantial positive inotropic effect (EC₅₀ = 0.25 mg/mL) but no change in the rate. The ethanol, chloroform and petroleum ether extracts all decreased the rate of contraction. A slight increase in force was seen with ethanol and chloroform extracts. Higher concentrations of the chloroform extract had a negative inotropic effect. The ethanol extract decreased the maximum following frequency of the left atria. It is concluded that Terminalia arjuna has a significant positive inotropic property on rat atria in vitro which could contribute to its efficacy in treating cardiovascular disorders.     

Saussurea costus: botanical, chemical and pharmacological review of an ayurvedic medicinal plant

Saussurea costus (Falc.) Lipschitz, syn Saussurea lappa C.B. Clarke is a well known and important medicinal plant widely used in several indigenous systems of medicine for the treatment of various ailments, viz. asthma, inflammatory diseases, ulcer and stomach problems. Sesquiterpene lactones have been reported as the major phytoconstituents of this species. Different pharmacological experiments in a number of in vitro and in vivo models have convincingly demonstrated the ability of Saussurea costus to exhibit anti-inflammatory, anti-ulcer, anticancer and hepatoprotective activities, lending support to the rationale behind several of its traditional uses. Costunolide, dehydrocostus lactone and cynaropicrin, isolated from this plant, have been identified to have potential to be developed as bioactive molecules. Due to the remarkable biological activity of Saussurea costus and its constituents it will be appropriate to develop them as a medicine. The present review is an up-to-date and comprehensive analysis of the botany, chemistry, pharmacology and traditional and folkloric uses of Saussurea costus.     

Modulating effect of Liv.100, an ayurvedic formulation on antituberculosis drug-induced alterations in rat liver microsomes

The influence of Liv.100 on the hepatotoxicity of antituberculosis drugs [isoniazid (INH), rifampicin (RMP) pyrazinamide (PZA)] was studied in male albino rats. INH, RMP, and PZA were proved to be the most hepatotoxic. Rats were treated with antituberculosis drugs daily for a period of 6 weeks by intragastric administration. The combined use of antituberculosis drugs elevated the levels of cytochrome P-450 and cytochrome-b5. A significant increase was observed in the levels of NADPH-cytochrome P-450 reductase and NADH-cytochrome-b5 reductases after antitubercular drug administration. During antitubercular drug treatment a significant decrease was also observed in the activity of glucose-6-phosphatase. The extent of NADPH-induced and ascorbic acid-induced lipid peroxides were marked in antitubercular drug treatment, when compared with normal control animals. Oral Liv.100 co-administration, for the same period, modulated the alterations in the xenobiotic metabolizing system and microsomal lipid peroxidation in experimental animals. The results are discussed with reference to drug metabolizing enzymes, lipid peroxidation and the hepatoprotective nature of Liv.100.     

In vitro antioxidant studies and free radical reactions of triphala, an ayurvedic formulation and its constituents

The aqueous extract of the fruits of Emblica officinalis (T1), Terminalia chebula (T2) and Terminalia belerica (T3) and their equiproportional mixture triphala were evaluated for their in vitro antioxidant activity. gamma-Radiation induced strand break formation in plasmid DNA (pBR322) was effectively inhibited by triphala and its constituents in the concentration range 25-200 microg/mL with a percentage inhibition of T1 (30%-83%), T2 (21%-71%), T3 (8%-58%) and triphala (17%-63%). They also inhibited radiation induced lipid peroxidation in rat liver microsomes effectively with IC(50) values less than 15 microg/mL. The extracts were found to possess the ability to scavenge free radicals such as DPPH and superoxide. As the phenolic compounds present in these extracts are mostly responsible for their radical scavenging activity, the total phenolic contents present in these extracts were determined and expressed in terms of gallic acid equivalents and were found to vary from 33% to 44%. These studies revealed that all three constituents of triphala are active and they exhibit slightly different activities under different conditions. T1 shows greater efficiency in lipid peroxidation and plasmid DNA assay, while T2 has greater radical scavenging activity. Thus their mixture, triphala, is expected to be more efficient due to the combined activity of the individual components.     

Studies on Ruta chalepensis, an ancient medicinal herb still used in traditional medicine

An ethanolic extract of the aerial parts of Ruta chalepensis was studied for its anti-inflammatory, antipyretic, analgesic and CNS depressant activities. The extract produced a significant inhibition of carrageenan-induced paw oedema and cotton pellet granuloma in rats. The studies on spontaneous motor activity in mice and conditioned avoidance responding (CAR) in rats showed a dose-dependent depression of the central nervous system in treated animals. Reduction of yeast-induced hyperthermia in mice confirmed its reputed antipyretic activity. The extract did not produce any significant changes in prothrombin time and fibrinogen level. It also failed to produce any analgesic activity in the hot plate reaction-time test in mice. Phytochemical screening of the aerial parts of the plant showed the presence of alkaloids, flavonoids, coumarins, tannins, volatile oil, sterols and/or triterpenes.     

Postnatal development and reproductive performance of F1 progeny exposed in utero to an ayurvedic contraceptive: Pippaliyadi yoga

The purpose of this study was to characterize the putative anxiolytic-like activity of an ethanolic extract prepared from the leaves of Apocynum venetum (AV) using the elevated plus maze (EPM) in mice. Male C75BL/6 mice were either treated orally with the AV extract or the positive controls diazepam and buspirone, respectively, 1 h before behavioral evaluation in the EPM. A single treatment of AV extract markedly increased the percentage time spent on and the number of entries into the open arms of the EPM in doses of 30 and 125 mg/kg p.o., respectively. This effect was comparable to that of the benzodiazepine diazepam (1.5 mg/kg p.o.) and the 5-HT_1A agonist buspirone (10 mg/kg p.o.). The effects of AV in 125 mg/kg were effectively antagonized by the benzodiazepine antagonist flumazenil (3 mg/kg i.p.). However, the effects of AV extract could only partially be blocked by the unspecific 5-HT_1A receptor antagonist WAY-100635 (0.5 mg/kg i.p.). Neither diazepam and buspirone nor the AV extract produced any overt behavioral change or motor dysfunction in the open field test. These results indicate that AV extract is an effective anxiolytic agent, and suggest that the anxiolytic-like activities of this plant are mainly mediated via the GABAergic system.     

Evolvulus alsinoides (Convolvulaceae): an American herb in the Old World

People in the Indian region often apply shankhapushpi and vishnukranti, two Sanskrit-based common names, to Evolvulus alsinoides. These are pre-European names that are applied to a medicinal American species transported into the area. The period of introduction is uncertain, but probably took place in the 1500s or 1600s. Examination of relationships of Evolvulus alsinoides, geographic distribution, its names in Asia, medical uses, and chemical and laboratory analysis indicates that the alien plant was adopted, given an ancient Indian name, and incorporated into some Old World pharmacopoeias. The herb apparently was included in medicines because it not only reminded people of certain aspects of their gods and goddesses, but also because the chemicals it contained were useful against some maladies.     

白癜风病机的神经内分泌免疫机制相关进展△

白癜风（vitiligo）为常见的后天性色素脱失性皮肤黏膜疾病,近年来发病率有上升趋势。其发病病因及机制上无定越来越多的证据表明其发生、发展与患者神经、内分泌、免疫等递质或细胞因子密切相关。本文就以上方面最新进行阐述,为白癜风的基础研究及治疗提供新的思路。     

Apocynum venetum leaf extract, an antihypertensive herb, inhibits rat aortic contraction induced by angiotensin II: A nitric oxide and superoxide connection

Ethnopharmacological relevance

The leaves extract of Apocynum venetum (AVLE), also known as “luobuma”, have long been used in traditional Chinese medicine to treat hypertension and depression in parts of China and it has been shown to possess anti-oxidant and anti-lipid peroxidation effects. AVLE (10 μg/ml) has been reported to have a long-lasting endothelium-dependent relaxant effect and this effect has been proposed to be due to its nitric oxide(NO)-releasing and superoxide anion(SOA)-scavenging properties.

Aim of the study

The present study seeks to evaluate the differential actions of AVLE extract between Ang II- and PE-induced vasoconstriction and the involvement of superoxide anions.

Materials and methods

Single dose of Ang II (100 nM and 1 nM)- or PE (0.1 μM)-induced contraction were assessed in both endothelium-intact and -denuded aortic rings after pre-incubation of AVLE (10 μg/ml) for 15 min. The experiment was repeated in either the presence of NO synthase inhibitor, l-NAME (300 μM) or selective AT₁ receptor inhibitor, losartan (0.1 nM), or superoxide scavenger, tiron (1 mM) or a combination of l-NAME and AVLE. Superoxide production was measured by using enhanced-chemiluminescence assay.

Results

We have demonstrated that AVLE (10 μg/ml) effectively suppressed the Ang II-induced contraction (100 nM and 1 nM) of both endothelium-intact and -denuded rat aortic rings. In endothelium-intact rings, l-NAME, reversed AVLE-induced inhibition of Ang II-contraction. PE-induced contraction was significantly inhibited by AVLE in endothelium-intact rings, but not in endothelium-denuded rings. The inhibition by AVLE of PE-induced contraction was totally abolished in the presence of l-NAME. Ang II-induced SOA production concentration dependently with the optimal effect seen at 100 nM of Ang II, and AVLE (0.3, 1, 10 μg/ml) reduced this effect. SOA production in Ang II-stimulated rings was significantly higher than unstimulated control rings, while PE did not stimulate SOA production at all. SOA formation in the presence of Ang II was also inhibited in the presence of SOD (superoxide scavenger), DPI (NADPH inhibitor) and losartan (specific AT₁ receptor antagonist).

Conclusion

These results collectively suggest that the ability of AVLE in inhibiting Ang II-induced contraction via its SOA scavenging properties and nitric oxide releasing effect may account for its usage as an antihypertensive treatment in traditional folk medicine.     

The evaluation of the radioprotective effect of chyavanaprasha (an ayurvedic rasayana drug) in mice exposed to lethal dose of gamma-radiation: a preliminary study

The effect of various doses of 50% ethanolic extract of chyavanaprasha (an Ayurvedic rejuvenating herbal preparation) was studied on the survival of mice exposed to 10 Gy of gamma-radiation. Treatment with chyavanaprasha, consecutively for fi ve days before irradiation, delayed symptoms of radiation sickness and onset of mortality when compared with the non-drug treated irradiated controls. All doses of chyavanaprasha provided a significant protection against gastrointestinal (GI) death (death of animals within 10 days after exposure to radiation), however, highest protection against GI death was observed for 15 mg/kg chyavanaprasha. Chyavanaprasha also provided a significant protection against the bone marrow death after 10 to 40 mg/kg. However, the best protection was seen for 15 mg/kg, where the highest number of survivors was observed at the end of 30 days post-irradiation. The drug was non-toxic up to a dose of 6 g/kg b. wt., the highest drug dose that could be tested. Our study demonstrates that chyavanaprasha can provide good radioprotection at a very low non-toxic dose.     

Effects of Kang-Jia-Wan,a Chinese medicinal herb officinal,on apoptosis induction in goiter of rats

Ethnopharmacological relevance

Kang-Jia-Wan (KJW), a traditional Chinese herbal medicine, is widely used to treat goiter in the clinics in China.

Aim

The mechanisms by which KJW treats goiter are unclear. It is known that insufficient apoptosis of thyrocytes is involved in the formation of goiter. Here, we investigated whether KJW could induce apoptosis in goiter of rats given methimazole (MMI).

Materials and methods

Fifty-six Wistar rats were randomly separated into four groups: normal, MMI, MMI + low-dose KJW and MMI + high-dose KJW. Except for the normal group (20 rats), all groups (each with 12 rats) were given 0.04% (w/v) MMI in their drinking water. One week later, the rats in MMI + low- and high-dose KJW groups were orally supplemented with KJW at 250 mg/kg d⁻¹ and 1000 mg/kg d⁻¹, respectively.

Results

After KJW treatment for 12 weeks, the relative thyroid weight (mg/100 g body weight) of the MMI + high-dose KJW group decreased significantly. Features of apoptosis were also apparent in thyroid tissues of rats given KJW treatment. Importantly, KJW markedly increased the caspase-3 and Fas protein expression, in a dose-dependent manner, in the thyroid specimens.

Conclusions

These results showed that KJW played a therapeutic role via apoptosis induction in the goitrous glands.     

麻黄汤中臣、佐、使药对君药中麻黄碱的人体内过程的影响

目的以君药效应成分麻黄碱为指标,采用GC-MS法考察不同配伍对麻黄碱药动学参数的影响规律,探索麻黄汤方中臣、佐、使药对君药在人体内过程的影响。方法对麻黄汤作正交设计拆成8个配伍组,每组8名健康男性志愿者,服药后在不同时间点抽取静脉血,测定血浆中麻黄碱,绘制药-时曲线;选用WinNonlin4.0.1软件求算药动学参数;采用SPSS10.0软件对药动学参数进行统计分析。结果药时曲线均符合无滞后开放式1房室动力学模型;不同配伍对麻黄碱的部分药动学参数有显著影响(P<0.05);方中各药味对麻黄碱的部分药动学参数的影响有显著交互作用(P<0.05)。结论臣、佐、使药对方中君药的有效成分麻黄碱的药动学参数有一定影响。