Ethnobotany,phytochemistry and pharmacology of Stephania rotunda Lour

Ethnopharmacological relevance

Stephania rotunda Lour. (Menispermaceae) is an important traditional medicinal plant that is grown in Southeast Asia. The stems, leaves, and tubers have been used in the Cambodian, Lao, Indian and Vietnamese folk medicine systems for years to treat a wide range of ailments, including asthma, headache, fever, and diarrhoea. Aim of the review: To provide an up-to-date, comprehensive overview and analysis of the ethnobotany, phytochemistry, and pharmacology of Stephania rotunda for its potential benefits in human health, as well as to assess the scientific evidence of traditional use and provide a basis for future research directions.

Material and methods

Peer-reviewed articles on Stephania rotunda were acquired via an electronic search of the major scientific databases (Pubmed, Google Scholar, and ScienceDirect). Data were collected from scientific journals, theses, and books.

Results

The traditional uses of Stephania rotunda were recorded in countries throughout Southeast Asia (Cambodia, Vietnam, Laos, and India). Different parts of Stephania rotunda were used in traditional medicine to treat about twenty health disorders. Phytochemical analyses identified forty alkaloids. The roots primarily contain l-tetrahydropalmatine (l-THP), whereas the tubers contain cepharanthine and xylopinine. Furthermore, the chemical composition differs from one region to another and according to the harvest period. The alkaloids exhibited approximately ten different pharmacological activities. The main pharmacological activities of Stephania rotunda alkaloids are antiplasmodial, anticancer, and immunomodulatory effects. Sinomenine, cepharanthine, and l-stepholidine are the most promising components and have been tested in humans. The pharmacokinetic parameters have been studied for seven compounds, including the three most promising compounds. The toxicity has been evaluated for liriodenine, roemerine, cycleanine, l-tetrahydropalmatine, and oxostephanine.

Conclusion

Stephania rotunda is traditionally used for the treatment of a wide range of ailments. Pharmacological investigations have validated different uses of Stephania rotunda in folk medicine. The present review highlights the three most promising compounds of Stephania rotunda, which could constitute potential leads in various medicinal fields, including malaria and cancer.     

Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials

Ethnopharmacological relevance

Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model.

Materials and Methods

The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages.

Results

The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition).

Conclusions

The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration.     

Effect of Bridelia ferruginea Benth (Euphorbiaceae) ethyl acetate and acetone fractions on insulin resistance in fructose drinking mice

Ethnopharmacological relevance

The root of Bridelia ferruginea is traditionally used as a treatment for type 2 diabetes. The present study was investigated to evaluate the effect of Bridelia ferruginea root bark fractions on some markers of type 2 diabetes on fructose drinking mice.

Materials and methods

Mice received a solution of fructose 15% during 42 days ad libitum; at the 15th day to the 42nd day, they received distilled water for fructose drinking control group, metformin 50 mg/kg per day or fractions 50 mg/kg per day for treatment groups. The normal control group received only distilled water during the experiment. After 6 weeks of experiment, OGTT, fasting blood glucose, plasma insulin, triglycerides (TG), total cholesterol, AST and ALT levels were measured.

Results

Fructose drinking control group (F) showed significant (p<0.001) increase of glucose tolerance, plasma levels of total cholesterol, triglycerides and insulin index for insulin resistance (Homeostasis Model Assessment ratio HOMA-IR) as compared to normal control mice. In treated groups, there was a significant reduction of glucose intolerance respectively 74% (p<0.001), 25% (p<0.5) and 92% (p<0.001) for ethyl acetate fraction, acetone fraction and metformin at the same dose of 50 mg/kg per day during 4 weeks administration. In ethyl acetate fraction and metformin treated groups, biochemical parameters and insulin index were significantly (p<0.001) lower than that of fructose drinking control group.

Conclusions

This indicates that Bridelia ferruginea root bark ethyl acetate fraction improved insulin resistance as metformin significantly in type 2 diabetes.     

The pharmacology of medieval sedatives: The “Great Rest” of the Antidotarium Nicolai

Ethnopharmacological relevance

Past practices of compound drugs from different plant ingredients enjoyed remarkable longevity over centuries yet are largely dismissed by modern science as subtherapeutic, lethal or fanciful.

Aim of the study

To examine the phytochemical content of a popular medieval opiate drug called the “Great Rest” and gauge the bioavailability and combined effects of its alkaloid compounds (morphine, codeine, hyoscyamine, scopolamine) on the human body according to modern pharmacokinetic and pharmacodynamic parameters established for these compounds.

Calculations and theory

We reviewed the most recent studies on the pharmacodynamics of morphine, codeine, hyoscyamine and scopolamine to ascertain plasma concentrations required for different physiological effects and applied these findings to dosage of the Great Rest.

Results

Given the proportional quantities of the alkaloid rich plants, we calculate the optimal dose of Great Rest to be 3.1±0.1–5.3±0.76 g and reveal that the lethal dose of Great Rest is double the therapeutic concentration where all three alkaloid compounds are biologically active.

Conclusion

This study helps establish the effective dose (ED₅₀), toxic dose (TD₅₀) and lethal dose (LD₅₀) rates for the ingestion of raw opium, henbane and mandrake, and describes their probable combined effects, which may be applied to similar types of pre-modern pharmaceuticals to reveal the empirical logic behind past practices.     

Pharmacokinetic comparisons of five ephedrine alkaloids following oral administration of four different Mahuang–Guizhi herb-pair aqueous extracts ratios in rats

Ethnopharmacological relevance

Herba Ephedra (Mahuang in Chinese), is derived from dried Ephedra sinica Stapf stems and has been widely used to treat the common cold, coughs, asthma, and edema for thousands of years. The Mahuang–Guizhi herb-pair is a famous formula composed of Mahuang and Ramulus Cinnamomi (Guizhi in Chinese, the dried twig of Cinnamomum cassia Presl.), used to improve pharmacological effects and reduce toxicity. In order to investigate the influence of Mahuang–Guizhi herb-pair ratios on bioavailability, the plasma pharmacokinetics profiles of five ephedrine alkaloids were compared following oral administration of four different ratios to rats.

Materials and methods

Sprague-Dawley rats were randomly assigned to four groups and orally administered Mahuang–Guizhi (ratios 3:0; 3:1; 3:2; 3:4, w/w). Assays for five ephedrine alkaloids (ephedrine, pseudoephedrine, methylephedrine, norephedrine, and norpseudoephedrine) were developed and validated using ultra-high-performance liquid chromatography tandem mass spectrometry coupled with liquid-liquid extraction.

Results

Key pharmacokinetic parameters of the five ephedrine alkaloids (maximal plasma concentration, mean residence time, and half-life) were significantly different (p<0.05) after oral administration of Mahuang–Guizhi herb-pair ratios, as compared to those of Mahuang.

Conclusion

Ephedrine alkaloid pharmacokinetic differences in rat plasma could help explain previous findings of pharmacological and toxicity differences between Mahuang and Mahuang–Guizhi herb-pair preparations. These results could facilitate future studies to increase the efficacy and decrease the toxicity of Mahuang and Guizhi.     

Terminalia arjuna in coronary artery disease: Ethnopharmacology,pre-clinical,clinical & safety evaluation

Ethnopharmacological relevance

Terminalia arjuna (Roxb.) Wight & Arn. is one of the most popular and beneficial medicinal plants in indigenous system of medicine for the treatment of cardiovascular diseases. This comprehensive review provides latest updates on traditional use, phytochemistry, pharmacological and toxicological data, clinical efficacy and safety of Terminalia arjuna as well as outlined strategies for future research and development to scientifically validate the therapeutic potential of this plant.

Materials and methods

Information about Terminalia arjuna was collected via a systematic electronic and library search of various indexed and non-indexed journals, some local books and varied articles published on ethnopharmacology, phytochemistry and traditional uses. Various pre-clinical (2000–2014) and clinical studies (1990–2014) have also been considered regarding efficacy and safety profile of Terminalia arjuna.

Results

Evidence from various in vitro, in vivo and clinical trials reveal the pleiotropic effects of Terminalia arjuna such as anti-atherogenic, hypotensive, inotropic, anti-inflammatory, anti-thrombotic and antioxidant actions for treatment of various cardiovascular disorders. It is clearly documented that this plant has a good safety profile when used in conjunction with other conventional drugs. However, there is a paucity of data regarding the exact molecular mechanism of its action, appropriate form of drug administration, whether whole crude drug or aqueous or alcoholic extract should be used, toxicological studies and its interaction with other drugs.

Conclusions

In conclusion, this review highlights the importance as well as pleiotropic actions and functional aspects of Terminalia arjuna especially in cardiovascular diseases. Though, various pharmacological studies and clinical trials support its benefit in the CVD as per traditional use, new clinical trials using more rigorous state of the art technology and in a larger population setup are warranted to assess the traditional putative efficacy of Terminalia arjuna.     

Effect of sulfated polysaccharides from Laminaria japonica on vascular endothelial cells in psychological stress rats

Ethnopharmacological relevance

Laminaria japonica is a popular seafood and medicinal plant in China. Laminaria japonica is used in traditional Chinese medicine to treat and prevent hypertension and edema.

Materials and methods

The vascular protective activity and mechanism of sulfated polysaccharides were studied in adrenalin-induced vascular endothelial damage in rats after psychological stress (PS). Vehicle (sham and PS groups), sulfated polysaccharide from Laminaria japonica (LP; 1 mg/kg and 5 mg/kg) and enoxaparin sodium (1 IU/kg, reference drug) were all administered for 10 days. Behavioral changes were recorded. Plasma levels of adrenalin, cortisol, monoamine oxidase (MAO), semicarbazide-sensitive amine oxidase (SSAO), formaldehyde, H₂O₂, nitric oxide (NO), endothelin-1 (ET-1), 6-keto-prostaglandin F_1a (6-keto-PGF_1a), and thromboxane B₂ (TXB₂) were measured. Endothelium-dependent relaxation of the thoracic aorta was measured and transmission electron microscopy of aortic vessels was performed.

Results

Adrenalin metabolites in plasma were significantly lower (P<0.01) in rats after LP administration compared with those in the PS groups. The normalized ratios of plasma NO/ET-1 and 6-keto-PGF_1a/TXB₂ were maintained and endothelium-dependent relaxation of the aorta was greatly enhanced after LP treatment (P<0.05). Morphological alterations were observed in vascular endothelial cells (VECs) in PS rats, with a higher number of lysosomes and vague mitochondrial cristae compared with those in the sham group. However, these histopathological changes were markedly alleviated after LP treatment.

Conclusions

This study shows a protective effect of LP on VECs in PS rats. LP can regulate plasma levels of NO, ET-1, and 6-keto-PGF_1a, enhance endothelium-dependent relaxation, and alleviate histopathological changes of lysosomes and mitochondria in VECs. The potential mechanism of LP on VECs in PS rats is related to its function of reducing metabolites of adrenalin.     

Protective effects of bajijiasu in a rat model of Aβ25-35-induced neurotoxicity

Ethnopharmacological relevence

Neurodegenerative diseases (NDs) caused by neurons and/or myelin loss lead to devastating effects on patients? lives. Although the causes of such complex diseases have not yet been fully elucidated, oxidative stress, mitochondrial and energy metabolism dysfunction, excitotoxicity, inflammation, and apoptosis have been recognized as influential factors. Current therapies that were designed to address only a single target are unable to mitigate or prevent disease progression, and disease-modifying drugs are desperately needed, and Chinese herbs will be a good choice for screening the potential drugs. Previous studies have shown that bajijiasu, a dimeric fructose isolated from Morinda officinalis radix which was used frequently as a tonifying and replenishing natural herb medicine in traditional Chinese medicine clinic practice, can prevent ischemia-induced neuronal damage or death.

Materials and methods

In order to investigate whether bajijiasu protects against beta-amyloid (Aβ_25-35)-induced neurotoxicity in rats and explore the underlying mechanisms of bajijiasu in vivo, we prepared an Alzheimer?s disease (AD) model by injecting Aβ_25-35 into the bilateral CA1 region of rat hippocampus and treated a subset with oral bajijiasu. We observed the effects on learning and memory, antioxidant levels, energy metabolism, neurotransmitter levels, and neuronal apoptosis.

Results

Bajijiasu ameliorated Aβ-induced learning and memory dysfunction, enhanced antioxidative activity and energy metabolism, and attenuated cholinergic system damage. Our findings suggest that bajijiasu can enhance antioxidant capacity and prevent free radical damage. It can also enhance energy metabolism and monoamine neurotransmitter levels and inhibit neuronal apoptosis.

Conclusion

The results provide a scientific foundation for the use of Morinda officinalis and its constituents in the treatment of various AD. Future studies will assess the multi-target activity of the drug for the treatment of AD.     

Prescription pattern of Chinese herbal products for hypertension in Taiwan: A population-based study

Ethnopharmacological relevance

Traditional Chinese medicine (TCM) has been commonly used in Asia country. The aim of this study is to analyze the utilization of TCM among hypertensive patients in Taiwan.

Materials and methods

The use of TCM for primary hypertensive patients was evaluated using a randomly sampled cohort of 1,000,0s recruited from the National Health Insurance Research Database in 5-year period from 2006 to 2010.

Results

Overall, 49.7% (n=42,586) of primary hypertension utilized TCM and 12.1% (n=5132) of them used TCM for the treatment of hypertension. Among the top 10 most frequently prescribed herbal formulae, Tian-Ma-Gou-Teng-Yin, Gout-Teng-San, Liu-Wei-Di-Huang-Wang and its derivatives were found to be the most common herbal formulae prescribed by TCM doctors for the treatment of hypertension in Taiwan.

Conclusion

This study showed the utilization pattern of Chinese herbal product in patients with hypertension. Further researches and clinical trials are needed to evaluate the efficacy of these Chinese formulae or its ingredients in treating hypertension.     

Interactions of pharmacokinetic profile of different parts from Ginkgo biloba extract in rats

Ethnopharmacological relevance

Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts.

Materials and methods

A selective and sensitive UPLC–MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF–WEF, FF–TLF, TLF–WEF and FF–TLF–WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T_1/2, T_max, C_max and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student?s t-test with P<0.05 as the level of significance.

Results

FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that C_max and AUC of six flavonoid aglycones in group FF–WEF, FF–TLF and FF–TLF–WEF had varying degrees of reduction in comparison with group FF, especially in group FF–TLF–WEF. On the contrary, the values of C_max, T_max and AUC of four flavonoid glycosides in group FF–TLF–WEF were significantly increased compared with those in group FF.

Conclusions

These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones.     

Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark Scutia buxifolia Reissek in mice

Ethnopharmacological relevance

Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as “coronilha” and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice.

Materials and methods

The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400 mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated.

Results

The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400 mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400 mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400 mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed.

Conclusion

Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute administration with high doses of ethyl acetate fraction from the stem bark Scutia buxifolia, suggest that repeated administration of this fraction plant can cause adverse hepatic, renal, and hematological effects.     

Electrical conductivity measurements of urine as a new simplified method to evaluate the diuretic activity of medicinal plants

Ethnopharmacological relevance

Diuretic plants are widely used in traditional medicine in many countries. However, many of these species have not been subjected to experimental studies to confirm that property. In this paper, a simple new method is proposed to evaluate the diuretic activity of plants. We define a new index that takes into account only the volume of urinary excretion and total ion concentration excreted obtained by specific electrical conductivity measurements.

Materials and methods

Urine was collected in a graduate cylinder during the 8 h after Artemisia thuscula (AT), Withania aristata (WA), Smilax canariensis (SC) and HCTZ oral administration to laboratory mice. To obtain the new index Diuretic Power (DP), we measured the specific electrical conductivity (κ) of the fresh urine samples. We calculated the concentration of a NaCl (or KCl) aqueous solution that has the same specific electrical conductivity as the urine sample. We multiplied this concentration by the corresponding urinary excretion volume, thus obtaining the total mEq. of electrolyte excreted “as if all were NaCl (or KCl)”. Finally, we divided these mEq. by those corresponding to the control to obtain the DP value.

Results

HCTZ showed a 40% increase in DP, with respect to the control group, independently of the doses used, and the studied plants produced an increase between 7 and 28%. DP values were compared with other common indexes, DI and SIi, showing that the variation sequence of the three indexes was the same for HCTZ, WA and SC.

Conclusions

A new and easy index, that we called diuretic power (DP), for estimating the diuretic activity of drugs or plants is proposed. It allows us to highlight diuretic effect with respect to a control value of a large amount of drugs or plants that had not been previously experimentally studied.     

Acute and sub-chronic toxicity profile of methanol leaf extract of Gouania longipetala in rats

Ethnopharmacological relevance

Gouania longipetala leaves are commonly used in folkloric medicine in Africa and other parts of the world for treatment of edema, febrifuges, veneral diseases, lumbago, heart diseases, diabetes mellitus malaria, etc. This study therefore evaluated safety profile of the methanol leaf extract of the plant using acute and sub-chronic studies in rat model.

Materials and methods

Acute toxicity test of the plant lasted for 48 h with oral administration of graded doses (100–4000 mg/kg) of Gouania longipetala extract (GLE) in rats. The rats were observed for signs of toxicity and death. The sub-chronic toxicity was evaluated by administration of different doses (2.5, 5 and 10 mg/kg) of GLE daily in feed for 90 days. On days, 30, 60 and 90, blood samples collected from the retro-orbital plexus of the eye of the rats were used for evaluation of serum biochemistry, hematology, lipid peroxidation and in vivo antioxidant activities. Histopathological evaluations of the kidney, liver, lungs and heart were also done.

Results

The acute toxicity test revealed no observable signs of toxicity or morbidity. Sub-chronic study showed that GLE significantly (p<0.05) increased relative liver weight on day 90 at 10 mg/kg. There were no significant variations in the hematological parameters of both GLE treated and untreated rats. The extract significantly (p<0.05) reduced total cholesterol, triglycerides, very low density lipoproteins and increased high density lipoproteins which was more prominent on day 90 at the dose of 10 mg/kg. The extract significantly (p<0.05) increased liver enzyme markers at the doses used. GLE also significantly (p<0.05) increased serum urea at the dose of 10 mg/kg on day 90. The extract caused dose-dependent and significant (p<0.05) increase in superoxide dismutase and decrease in malondiadehyde. Histopathological studies revealed degenerative changes in the kidney and liver.

Conclusion

The results of the study suggest that Gouania longipetala is well tolerated in short term therapies, but may have long term toxic effects on the kidney and liver.     

Evaluation of hemostatic activity of latex from three Euphorbiaceae species

Ethnopharmacological relevance

Latices from several plant species of Euphorbiaceae family have been traditionally applied over fresh cuts to stop bleeding and subsequently applied over wounds to enhance healing process. The latex arrested bleeding from fresh wounds by reducing bleeding and whole blood coagulation time which are important indices of hemostatic activity. It has been accepted that hemostatic activity is due to the proteolytic fraction of plant latices. Thus, the present study aimed to assess the clot inducing properties of three Euphorbiaceae plants viz., Euphorbia nivulia Buch.-Ham., Pedilanthus tithymaloides (L.) Poit and Synadenium grantii Hook F.

Materials and methods

In the present study, various proteolytic activities namely protease, gelatinase, milk clotting and whole blood clotting assay of the enzyme fraction of latices of Euphorbia nivulia, Pedilanthus tithymaloides and Synadenium grantii have been investigated. The inhibition profile of protease specific inhibitors was assessed. Also, the effects of protein fractions were studied using bleeding/clotting time test of fresh experimentally-induced wounds in mice.

Results

Euphorbia nivulia latex protease has noticeable blood clotting activity followed by Pedilanthus tithymaloides and Synadenium grantii. Stem latex protease of Pedilanthus tithymaloides exhibits superior procoagulant activity in different mammal's blood samples viz., Capra hircus, Bubalus bubalis, Ovibos moschatus and Bos indicus. Blood sample of ox was the most sensitive to latex protease than other mammal's blood. Concomitantly, the plant latex protease could significantly reduce whole blood clotting time of human and mice blood samples.

Conclusion

The protease fraction of latices of Euphorbia nivulia, Pedilanthus tithymaloides and Synadenium grantii possesses phytoconstituents capable of arresting wound bleeding, and accelerating whole blood coagulation process. It suggests good potentiality for use of latex proteases in wound management. Also, the finding of this study showed that the protease enzyme of Pedilanthus tithymaloides has the most potent hemostatic agent.     

Clerodendrum serratum (L.) Moon. – A review on traditional uses,phytochemistry and pharmacological activities

Ethnopharmacological relevance

Clerodendrum serratum (L.) Moon. (Verbenaceae) is an important medicinal plant growing in the tropical and warm temperate regions like Africa, Southern Asia; Malaysia and distributed throughout in forests of India and Sri Lanka. It is traditionally valued and reported for treating pain, inflammation, rheumatism, respiratory disorders, fever and malarial fever in India with a long history. To provide a comprehensive overview of the traditional and ethno medicinal uses, phytochemistry and biological activities of C. serratum with clinical and toxicity data and possibly make recommendations for further research.

Materials and methods

All relevant worldwide accepted databases were searched for the terms “Clerodendrum”, “Clerodendrum serratum”, “Bharangi” and “Cheruthekku” along with the other literature from Indian classical texts and pharmacopoeias. There was no specific timeline set for the search. The accessible literatures available on C. serratum were collected via electronic search using Pubmed, Scopus, Science Direct and traditional books reports on ethnopharmacology and traditional medicines.

Results

C. serratum has played an important role in Indian system of medicine. In addition to the common local use in respiratory diseases, other ethnomedicinal uses include treatment of pain, inflammation, rheumatism and fever especially malarial fever. Scientific studies on extracts and formulations revealed anti-asthmatic, mast cell stabilization and anti-allergic effects of roots of C. serratum. Reported data on pharmacological activities also includes hepatoprotective, anti-oxidant, anti-inflammatory and anticancer potential of the drug. Saponins (terpenoids and steroids), flavonoids and phenolics isolated from roots have been the focus of phytochemical investigations as the biological activity has been ascribed to the saponins, which are known to possess anti-inflammatory and anti-cancer activity. Isolated bioactives from roots like icosahydropicenic acid and ursolic acid have been claimed to offer anti-allergic and hepatoprotective activity.

Conclusions

Therapeutic potential of roots and leaves of C. serratum has been demonstrated in the conditions like asthma, allergy, fever, inflammation and liver disorders attributed to the presence of various flavonoids, phenolics and saponins present in the drug. Many ethnobotanical claims have been confirmed through modern in-vitro and in-vivo pharmacological studies of different extracts and isolates from plant; however, additional studies on the biomarkers are needed to establish mechanism of action and to validate the traditional use of this drug in clinical practices after proper safety assessment.     

Hempseed oil induces reactive oxygen species- and C/EBP homologous protein-mediated apoptosis in MH7A human rheumatoid arthritis fibroblast-like synovial cells

Ethnopharmacological relevance

The medicinal efficacy of hempseed (Cannabis sativa L.), which is rich in polyunsaturated fatty acids, in atopic dermatitis, inflammation, and rheumatoid arthritis (RA) has been suggested for centuries. Hempseed has been used as a treatment for these diseases in Korean and Chinese folk medicine. The aim of the study is to investigate the effects of hempseed oil (HO) on MH7A human RA fibroblast-like synovial cells.

Materials and methods

MH7A cells were used to study the anti-rheumatoid effects of hempseed (Cannabis sativa L., cv. Cheungsam/Cannabaceae) oil by investigating cell viability, apoptosis, lipid accumulation, oxidative stress, and endoplasmic reticulum (ER) stress-induced apoptosis.

Results

HO treatment reduced the survival rate of MH7A cells and promoted apoptotic cell death in a time- and dose-dependent manner. Both lipid accumulation and the level of intracellular reactive oxygen species (ROS) increased in HO-treated MH7A cells. Co-treatment with the antioxidant Tiron effectively abrogated the cytotoxic effects of HO; the ROS level was reduced, cell viability was recovered, and apoptotic cell death was significantly diminished. Moreover, HO-treated cells exhibited increased expression of the major ER stress markers, glucose-regulated protein 78 and C/EBP homologous protein (CHOP). The siRNA-mediated knockdown of CHOP prevented HO-induced apoptosis.

Conclusions

Our results suggest that HO treatment induced lipid accumulation, ROS production, CHOP expression, and apoptosis in MH7A cells, and that CHOP functions as an anti-rheumatoid factor downstream of HO in MH7A cells.     

Confocal mirco-Raman spectroscopic analysis of the antioxidant protection mechanism of the oligosaccharides extracted from Morinda officinalis on human sperm DNA

Ethnopharmacological relevence

Male infertility is a stressful and frustrating problem for the society, but a number of male infertility treatments are available as traditional Chinese medicine strategies which have been tried with variable success, while evidence is still limited on whether-or how much-herbs or supplements might help increase fertility, so the aim of this study was to investigate if the oligosaccharides extracted from Morinda officialis, a Chinese herb, is the active constituents to the fertility.

Materials and methods

In this study, we prepared the H₂O₂-demaged human sperm, cocultured with the oligosaccharides in vitro, then observed the changes of the DNA using confocal micro-Raman spectroscopy, and comparative analysis the differences of the spectra of different treated groups.

Results

The results showed that the oligosaccharides extracted from Morinda officialis can keep the “Raman fingerprints” of the human sperm DNA almost the same as those of the control groups, but very different from the H₂O₂-induced groups, especially the intensity of bands at 787, 993, 1094, 1254, 1340, 1376, 1421, 1443, 1487, 1577 and 1662 cm⁻¹ which could be as potential targets for the drugs finding, and further principal component analysis was successfully used to classify the Raman spectra of normal control and model groups.

Conclusion

This results suggested that the oligosaccharides can protect the DNA of human sperm from being damaged by H₂O₂, and which was one of the active constituents of Morinda officialis on treating infertility. It was also demonstrated that Morinda officialis as a tonifying and replenishing natural herb medicine can be used to enhance reproductive functions, and the Raman spectroscopy could be an applicable technology for screening active components in vitro from herbs.     

Bioactive compounds from Cornus officinalis fruits and their effects on diabetic nephropathy

Ethnoparmacological relevance

The fruit of Cornus officinalis, called “Shanzhuyu”, a traditional medicine in China, is used for the treatment of kidney diseases, including diabetic nephropathy. The aim of this study is to investigate the anti-diabetic nephropathy activity of Shanzhuyu and the active compounds in the fruit.

Materials and methods

The air dried fruit of Cornus officinalis was extracted in 80% EtOH, the obtained residue was fractioned on D101 resin column eluted with H₂O/EtOH solution to get five crude fractions (fr. A–E). The anti-diabetic nephropathy activity of fractions (fr. A–E) was evaluated in vitro by inhibiting the expression of collagen IV (Col V), fibronectin (FN) and IL-6 in high-glucose-induced mesangial cells. By preliminary bio-assay screenings, repeated column chromatography on fraction B–D led the isolation of 22 compounds, whose structures were determined by extensive spectroscopic analysis, and the anti-diabetic nephropathy activity of the isolated compounds was also evaluated.

Results

Two new iridoid glucosides, logmalicids A and B (1 and 2), together with 20 known compounds (3–22) were isolated from the extract of Shanzhuyu under the bioassay-guided screenings. The anti-diabetic nephropathy activity assay displayed that fractions A, D and E could significantly inhibit the production of Col IV; fractions A and C could significantly inhibit the expression of FN and IL-6 in the high-glucose-stimulated mesangial cells at concentration of 50 μg/mL; and loganin (3) and its derivatives (1 and 2) could significantly inhibit the expression of FN and IL-6 at concentration of 10 μM, respectively.

Conclusions

The results suggested that loganin and its derivatives were the active compounds in Cornus officinalis fruit (Shanzhuyu) on diabetic nephropathy. This study further supported the traditional use of Shanzhuyu to treat diabetic nephropathy and related kidney diseases.     

Cyto-/genotoxic effects of the ethanol extract of Chan Su,a traditional Chinese medicine,in human cancer cell lines

Ethnopharmacological relevance

Chan Su, an ethanolic extract from skin and parotid venom glands of the Bufo bufo gargarizans Cantor, is widely used as a traditional Chinese medicine for cancer therapy. Although the anti-cancer properties of Chan Su have been investigated, no information exists regarding whether Chan Su has genotoxic effects in cancer cells. The aim of the present study was to examine the cyto-/genotoxic effect of Chan Su in human breast carcinoma (MCF-7 cells), human lung carcinoma (A-549 cells), human T cell leukemia (Jurkat T cells), and normal human lymphocytes.

Materials and methods

Effects on the viability of MCF-7, A-549, Jurkat T cells, and normal lymphocytes were evaluated by Trypan blue exclusion assays. The DNA content in the sub-G1 region was detected by propidium iodide (PI) staining and flow cytometry. The genotoxicity of Chan Su was assessed by single-cell gel electrophoresis (comet assay) and the cytokinesis-block micronucleus assay (CBMN assay).

Results

Chan Su significantly inhibited the viability of MCF-7, A-549, and Jurkat T cells dose dependently, but had no effect on normal human lymphocytes. Apoptotic death of the cancer cells was evident after treatment. Chan Su also induced genotoxicity in a dose-dependent manner, as indicated by the comet and cytokinesis-block micronucleus assays.

Conclusions

These findings suggest that Chan Su can induce apoptotic death of, and exert genotoxic effects on, MCF-7, A-549, and Jurkat T cells.