A review on the pharmacological and toxicological aspects of Datura stramonium L.

Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In Eastern medicine, especially in Ayurvedic medicine, D. stramonium has been used for curing various human ailments, including ulcers, wounds, inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma and bronchitis, and toothache. A few previous studies have reported on the pharmacological effects of D. stramonium; however, complete information regarding the pharmacology, toxicity, ethnobotany and phytochemistry remains unclear. Ethnomedicinally, the frequent recreational abuse of D. stramonium has resulted in toxic syndromes. D. stramonium, in the form of paste or solution to relieve the local pain, may not have a deleterious effect; however, oral and systemic administration may lead to severe anticholinergic symptoms. For this reason, it is very important for individuals, mainly young people, to be aware of the toxic nature and potential risks associated with the use of this plant. This comprehensive review of D. stramonium includes information on botany, phytochemistry, pharmacology, toxicology and ethnomedicinal uses.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

Objective: To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai(AGNE) on dextran sulfate sodium(DSS)-induced murine ulcerative colitis(UC).Methods: The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-a, PGE2, COX-2 and HIF-1 a were assayed by enzymelinked immunosorbent assay or western blotting.Results: Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss,decreased disease activity index scores, and reduced colon shortening in mice with DSSinduced UC. AGNE inhibited the production of IL-6 and TNF-a in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1 a and the increased production of PGE2 in colon tissue were observed in mice with DSSinduced UC. Additionally, histological damage was also alleviated by AGNE treatment.Conclusions: The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Effects of Angelica sinensis on longitudinal bone growth rate in adolescent female rats

OBJECTIVE To investigate the effect of A.sinensis on longitudinal bone growth rate in adolescent female rats.METHODS A.sinensis was extracted with 30% EtOH for 3h at 90℃in a reflux apparatus.Female Sprague-Dawley rats(33d-old)were randomly divided into three groups:control(vehicle),recombinant human growth hormone(rhGH;20μg·kg-1·d-1),and A.sinensis(300mg·kg-1·d-1).A.sinensis extracts or vehicle was administered orally twice daily for 4d.Longitudinal bone growth rate in newly synthesized bone was observed using tetracycline labeling(20mg·kg-1,intraperitoneally).RESULTS A.sinensis significantly increased longitudinal bone growth rate in adolescent female rats at 300mg·kg-1(6.1%,357.34±32.67μm·d-1)compared to control group(336.80±14.47μm·d-1).CONCLUSION A.sinensis extract significantly increased longitudinal bone growth rate and growth plate height in adolescent female rats.These results suggest that A.sinensis could be helpful for increasing bone growth rate in children who have growth retardation.

Effect of Dioscorea batatas on longitudinal bone growth rate in adolescent female rats

OBJECTIVE The root of Dioscorea batatas,rich in steroidal saponins,alkaloids,tannins,phytosterols,and starch,is an herbal medicine of tonifying qi and nourishing stomach after invigorating spleen with a long history of safe use for treatment of chronic dysentery and weakness of the spleen and stomach in Korea.This study was aimed to investigate the effect of D.batatas on longitudinal bone growth rate in adolescent female rats.METHODS D.batatas was extracted with 30% EtOH for 3h at 90℃in a reflux apparatus.In two groups,we administered a twice daily dosage of D.batatas extract(at 30 and 300mg·kg-1,respectively)per os for 4d,and in a control group,we administered vehicle only under the same conditions.Recombinant human growth hormone(rhGH)was subcutaneously injected once daily.All rats were born at same day(33d-old).On day 3,tetracycline was injected intraperitoneally to form a fluorescent band on the growth plates.RESULTS The bone growth rate in groups administered D.batatas 300mg·kg-1 and rhGH was significantly increased to 343.8±20.7,and 359.6±30.2μm·d-1 respectively from control group,320.7±23.2μm·d-1.No difference was observed in the amount of food intake or mean body weight among all groups during the acclimation or administration period.CONCLUSION These results suggest that D.batatas extracts have the potential to induce height increase;however,further research,including clinical trials,is necessary.

Testa of Rhynchosia nulubilis down-regulates melanin synthesis in UVB-induced guinea pigs epidermal skin tissue

OBJECTIVE Synthetic compounds that are used in the clinic to regulate skin hyperpigmentation,such as arbutin,and kojic acid,are only moderately effective.But their use is limited by side effects.As part of an effort to overcome the limitations,there is a pressing need for developing effective natural product for whitening.Each of black soybean has been reported to produce anti-melanogenic effects.Especially,antioxidant and anti-aging compounds are richer in testa than the rest part of black soybean.Therefore,we hypothesized that testa of Rhynchosia nulubilis(TR)would show more anti-melanogenic effects than whole black soybean.METHODS Anti-melanogenic effect of TR was done by using mouse B16F10 melanoma.The depigmenting efficacy was then observed following topical application of the TR to UVB-stimulated hyperpigmented dorsal skin of guinea pigs.RESULTS Treatment with TR extract resulted a 27.67% decrease in melanogenesis while whole black soybean showed 5.3% decrease at mouse melanoma cell line.Colorimetric analysis showed a significantly lower depigmenting value by day 14 following treatment with TR in UVB-irradiated guinea pigs the dorsal skin,indicating that TR produced a depigmentation effect.By staining with Hematoxylin-Eosin staing and Fontana-Masson stain,we found that the TR-treated group had more effect histopathologically in epidermal melanin production than resveratrol or rice alone-treated group.TR was associated with reduction in the levels of microphthalmia-associated transcription factor(MITF),and downregulation of tyrosinase and tyrosinase-related protein(TRP-1)expression,leading to inhibit epidermal melanin production by Western blotting analysis.CONCLUSION This study suggests that the testa of R.nulubilis may be a promising candidate in regulating skin pigmentation with UVB exposure.

Inhibitory activity of Cinnamomum Cassia extract on hypersensitivity in mice

OBJECTIVE Cinnamomum cassia has been used in traditional medicine in East Asian countries to treatallergic disease.Previous studies have demonstrated that C.cassiainhibits the development of mite antigen-induced skin lesions in NC/Nga mice by suppressing the Thelper 2cell response.The objective of this study is to investigate whether C.cassia has an efficient inhibition on systemic anaphylaxis and contact hypersensitivity in mice.METHODS To induce systemic anaphylaxis,mice were injected intraperitoneally with compound 48/80.Mortality was monitored for 1h after the injection.Contact hypersensitivity reaction was induced by topical application of 2,4-dinitrofluorobenzene(DNFB)to the ears of mice.After DNFBchallenge,ear thickness was measured 0,24 and 48h.RESULTS We discovered that C.cassia significantly inhibited compound 48/80-induced anaphylaxis and DNFB-induced ear swelling.Compound 48/80-induced anaphylaxiswas completely inhibited at the dose of 60mg·kg-1 body weight.Ear swelling at 24 h after DNFB-challenge was significantly less than that in the control group(0.16±0.03 vs.0.32±0.03 mm,P<0.01),while C.cassia was administered at the dose of 200mg·kg-1.CONCLUSION These findings indicate that C.cassiasuppresses allergic reactions,thus has potential value for mitigation of atopic dermatitis.

Therapeutic Effects of Traditional Herbal Medicine on Cerebral Ischemia:A Perspective of Vascular Protection

Although many agents for acute ischemic stroke treatment have been developed from extensive preclinical studies, most have failed in clinical trials. As a result, researchers are seeking other methods or agents based on previous studies. Among the various prospective approaches, vascular protection might be the key for development of therapeutic agents for stroke and for improvements in the efficacy and safety of conventional therapies. Traditional medicines in Asian countries are based on clinical experiences and literature accumulated over thousands of years. To date, many studies have used traditional herbal medicines to prove or develop new agents based on stroke treatments mentioned in traditional medicinal theory or other clinical data. In the current review, we describe the vascular factors related to ischemic brain damage and the herbal medicines that impact these factors, including Salviae Miltiorrhizae Radix, Notoginseng Radix, and Curcumae Rhizoma, based on scientific reports and traditional medical theory. Further, we point out the problems associated with herbal medicines in stroke research and propose better methodologies to address these problems.

Vasorelaxant effects of 50 commonly used traditional herbal prescriptions on isolated rat aortic rings

OBJECTIVE:To investigate the vasorelaxant activities of 50 common traditional herbal prescriptions(THPs)on isolated rat aortic rings.METHODS:An electric extractor was used to extract THPs.Rat aortic rings were precontracted using phenylephrine in organ chambers containing Krebs-Henseleit solution.Decoctions of THPs were added in increasing concentrations(10-1000μg/mL)to investigate vasorelaxant activities.The vasorelaxant effects of THPs were calculated as percentage of contraction in response to phenylephrine.RESULTS:Several THPs such as Tianwangbuxin Dan,Banxiaxiexin Tang,and Mahuang Tang,significantly relaxed precontracted aortic rings.In contrast,Xiaochaihu Tang,Shensuyin,and Guizhifuling Wan significantly contracted aortic rings.Furthermore,these THPs increasingly relaxed or contracted aortic rings relaxed by amlodipine.CONCLUSION:Our findings suggest that hypertension can be treated using THPs.However some THPs can counteract treatment of hypertension.Further studies should be developed on use of THPs for treatment of hypertension are critical,and guidelines for use of traditional herbal medicines to treat hypertension.

Herbal Medicine in Ischemic Stroke:Challenges and Prospective

Herbal medicines, mainly of plant source, are invaluable source for the discovery of new therapeutic agents for all sorts of human ailments. The complex pathogenesis of stroke and multifactorial effect of herbal medicine and their active constituents may suggest the promising future of natural medicine for stroke treatment. Anti-oxidant, anti-inflammatory, anti-apoptotic, neuroprotective and vascular protective effect of herbal medicines are believed to be efficacious in stroke treatment. Herbs typically have fewer reported side effects than allopathic medicine, and may be safer to use over longer period of time. Herbal medicines are believed to be more effective for the longstanding health complaints, such as stroke. Several medicinal plants and their active constituents show the promising results in laboratory research. However failure in transformation of laboratory animal research to the clinical trials has created huge challenge for the use of herbal medicine in stroke. Until and unless scientifically comprehensive evidence of the efficacy and safety of herbal medicine in ischemic stroke patients is available, efforts should be made to continue implementing treatment strategies of proven effectiveness. More consideration should be paid to natural compounds that can have extensive therapeutic time windows, perfect pharmacological targets with few side effects. Herbal medicine has excellent prospective for the treatment of ischemic stroke, but a lot of effort should be invested to transform the success of animal research to human use.

Neuroprotective effects of Fructus Chebulae extracts on experimental models of cerebral ischemia

OBJECTIVE:To investigate the neuroprotective effects of Fructus Chebulae extract using both in vivo and invitromodels of cerebral ischemia.METHODS:As an in vitro model,oxygen glucose deprivation followed by reoxygenation(OGD-R)and hydrogen peroxide(H2O2)induced cellular damage in rat pheochromocytoma(PC12)cells was used to investigate the neuroprotective effects of extract of Fructus Chebulae.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to calculate cell survival.For in vivo,occlusion of left middle cerebral artery on rats was carried out as a focal cerebral ischemic model.RESULTS:Fructus Chebulae extract increases the PC12 cell survival against OGD-R and H2O2by 68%and 91.4%respectively.Fructus Chebulae also de-creases the cerebral infarct volume by 39%and extent of hemisphere swelling from 17%in control group to 10%in FructusChebulaetreated group.CONCLUSION:Fructus Chebulae,as a traditional medicine,can rescue the neuronal cell death against ischemia related damage.The possible mechanism for the neuroprotection might be the inhibition of oxidative damages occurring after acute phase of cerebral ischemia.

Review on the characteristics of liver-pacifying medicinal in relation to the treatment of stroke: from scientific evidence to traditional medical theory

OBJECTIVE： To analyze the characteristics of liver pacifying medicinal in the treatment of brain disease to provide scientific evidence in clinical usage on stroke.METHODS： MEDLINE/PubMed, Google Scholar, and China National Knowledge Infrastructure Database were used as the literature sources. The Scientific name, Latin pharmaceutical name, Chinese name of 7 kinds of liver pacifying medicinal including Gouteng （Ramulus Uncariae Rhynchophyllae cure Uncis）, Tianma （Rhizoma Gastrodiae）, Juemingzi （Semen Cassiae Obtusifoliae）, Quanxie （Scorpio）, Wugong （Scolopendra）, Jiangcan （Bombyx Batryticatus）, and Dilong （Pheretima Aspergillum） were used as the keywords to search the databases for relevant publications up to July 2016. Their major compounds were also used as the keywords. The papers were selected based on the pharmacological activities and mechanisms of action related to brain diseases and subsequently, were analyzed and reviewed. We first described the origin, efficacy, and clinical indications of selected medicines, then brain disease specific activities focusing on stroke after the description of the general pharmacological activities. RESULTS： On the basis of the literature of scientific studies and clinical use in traditional medicine, we found and discussed the characteristics of liver pacifying medicinal in stroke treatment. First, liver-pacifying medicinal, or their components, might pass through the blood-brain barrier and act directly on neurons or on the neural network to provide protective effects against brain disease. Second, although it could be used throughout the disease duration, treatment of stroke might be more effective from the subacute up to the convalescent phase than the acute phase.CONCLUSION： We can suggest that live pacifying medicinal has beneficial pharmacological activities directly or indirectly on neurons in brain disease and is useful for the treatment of stroke from subacute to convalescent phase.

Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris(AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC(200 mg·kg-1) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.

Safety of acupotomy in a real-world setting:A prospective pilot and feasibility study

Objective:Acupotomy is a modern acupuncture method that includes modern surgical methods.Since acupotomy is relatively more invasive than filiform acupuncture treatment,it is important to establish the safety profile of this practice.To justify further large-scale prospective observational studies,this preliminary study was performed to assess the feasibility of the approach and investigate the safety profile and factors potentially associated with adverse events(AEs).Methods:This was a prospective pilot study that assessed the feasibility of a large-scale forthcoming safety study on acupotomy treatment in a real-world setting.The feasibility(call response rate,dropout rate,response rate for each variable and recruitment per month)and safety profile(incidence,type,severity and causality of AEs,and factors potentially associated with AEs)were measured.Results:A total of 28 participants joined the study from January to May 2018.A follow-up assessment was achieved in 258(1185 treatment points)out of 261 sessions(1214 treatment points).The response rate via telephone on the day after treatment was 87.3%.There were 8 systemic AEs in all the sessions(8/258;3.11%)and 27 local AEs on the total points treated(27/1185;2.28%).Severe AEs did not occur.Total AE and local AE occurrence were associated with blade width and the number of needle stimulations per treatment point.Conclusion:The findings suggest that it could be feasible to analyze the safety of acupotomy in a realworld setting.Moreover,the primary data on some relevant AEs could be determined.We are planning large-scale prospective studies based on these findings.Trial registration:Clinical Research Information Service(CRIS)KCT0002849(https://cris.nih.go.kr/cris/search/detailSearch.do/11487).

Scutellaria baicalensis in Stroke Management:Nature's Blessing in Traditional Eastern Medicine

Scutellaria baicalensis Georgi is the most widely used medicinal plant in traditional Eastem medicine, especially in Chinese medicine. The major phytochemicals isolated from S. baicalensis are flavonoids, glycosides and their glucoronides such as baicalin, baicalein, wogonin etc. More than 30 different kinds of flavonoids are isolated from this plant. S. baicalensis and its flavonoids are reported to have several pharmacological activities, which includes anti-allergic, antioxidant, anti apoptic, anti-inflammatory effects and many more. Recently, S. baicalensis and its isolated flavonoids have been studied for their neuroprotective effects, through a variety of in vitro and in vivo models of neurodegenerative diseases, plausibly suggesting that S. baicalensis has salutary effect as a nature＇s blessing for neuroprotection. In this review, we are focousing on the neuroprotective effects of S. baicalensis and its flavonoids in ischemia or stroke-induced neuronal cell death. We aimed at compiling all the information regarding the neuroprotective effect of S. baicalensis in various experimental models of cerebral ischemia or stroke.

Amomum villosum induces longitudinal bone growth in adolescent female rats

OBJECTIVE:This study was conducted to evaluate the effect of Amomum villosum on longitudinal bone growth.METHODS:Adolescent female Sprague-Dawley rats were divided into 3 groups and treated for 4 days:control(distilled water,p.o.),recombinant human growth hormone(rhGH;100 μg/kg,s.c.),and A.villosum(500 mg/kg,p.o.) groups.On day 3,tetracycline(20 g/kg,i.p.) was injected for growth plate identification.On days 2,3 and 4,5-bromo-2'-deoxyuridine(BrdU)(50 mg/kg,i.p.) was injected to label proliferating cells.On day 5,tibias were dissected and fixed in 4% paraformaldehyde,dehydrated,and sectioned for immunohistochemistry and histomorphometry.RESULTS:The rate of bone growth in the A.villosum and rhGH groups increased to(410 ± 44) and(389 ± 46) μm/day(P<0.01),respectively,as compared with the control(330.7 ± 34.7) μm/day.The thickness of the growth plates also increased to(591 ± 37) and(598 ± 32) μm,respectively,as compared with the control(524± 89) μm(P<0.001).The number of BrdU-positive cells in the chondrocytes of the A.villosum and rhGH groups was also significantly higher(126±24) and(143±18) cells/mm 2,respectively) than in the control(109 ± 25) mm 2(P<0.05).Insulin-like growth factor-1 and bone morphogenetic protein-2 in the A.villosum and rhGH groups were highly expressed in the growth plate as compared with the control samples,indicating increased bone formation.CONCLUSIONS:A.villosum could be used to treat growth retardation during adolescence.

Hydrangeae Dulcis Folium Attenuates Physical Stress by Supressing ACTH-Induced Cortisol in Zebrafish

Objective:To determine the effects of Hydrangeae Dulcis Folium(EHDF)on physical stress,changes in the whole-body cortisol level and behaviour in zebrafish(Danio rerio).Methods:One hundred and seventy-four fish were randomly divided into 4[adrenocorticotropin hormone(ACTH)challenge test:4 fish per group]or 6 groups(behavioural test:10–12 fish per group,whole-body cortisol:4 fish per group).Net handling stress(NHS)was used to induce physical stress.Fish were treated with vehicle or EHDF(5–20 mg/L)for 6 min before they were exposed to stress.And then,fish were sacrificed for collecting body fluid from whole-body or conducted behavioural tests,including novel tank test and open field test,and were evaluated to observe anxiety-like behaviours and locomotion.In addition,to elucidate the mode of action of the anti-stress effects of EHDF,ACTH(0.2 IU/g,i.p.)challenge test was performed.Results:The increased anxiety-like behaviours in novel tank test and open field test under stress were prevented by treatment with EHDF at 5–20 mg/L(P<0.05).Moreover,compared with the unstressed group,which was not treated with NHS,the whole-body cortisol level was significantly increased by treatment with NHS(P<0.05).Compared with the NHS-treated stressed control group,pre-treatment with EHDF at concentrations of 5–20 mg/L for 6 min significantly prevented the NHS-increased whole-body cortisol level(P<0.05).In addition,ACTH challenge test showed that EHDF completely blocked the effects of ACTH on cortisol secretion(P<0.05).Conclusion:EHDF may be a good antistress candidate and its mechanism of action may be related to its positive effects on cortisol release.