Effect of Alstonia scholaris bark extract on testicular function of Wistar rats

Abstract Aim: To evaluate the antifertility effect ofAlstonia scholaris bark extract in male rats. Methods: In male Wistar rats Alstonia scholaris bark extract was given by oral route at a dose of 200 mg/day for 60 days. The fertility and testicular function were assessed by mating tests, sperm motility, sperm concentration, biochemical indices and testicular cell population dynamics. Results: Oral feeding with the extract at a dose of 200 mg/day for the period of 60 days did not cause body weight loss, while the weights of testes, epididymides, seminal vesicle and ventral prostate were significantly reduced. The production of step-19 spermatids was reduced by 79.6% in treated rats. The population of preleptotene and pachytene spermatocytes were decreased by 61.9% and 60.1%, respectively. Spermatogonia and Sertoli cell population were also affected. The seminiferous tubule and Leydig cell nuclear area were reduced significantly (P<0.01) when compared to the controls. Reduced sperm count and motility resulted in a total suppression of fertility. A significant fall in the protein and sialic acid content of the testes, epididymides, seminal vesicle and ventral prostate as well as glycogen content of testes were also noticed. The fructose content in the seminal vesicle was lowered whereas the testicular cholesterol was elevated as compared with the controls. The following compounds were obtained from the extract with chromatographic separation over Si-gel column: α-amyrin, β-amyrin, lupiol acetate, venenative, rhazine and yohimbine. Conclusion: At the dose level employed, Alstonia scholaris bark extract has a significant antifertility effect in male rats; the primary site of action may be post meiotic germ cells (Step 19 spermatids).

Monoterpenoid Indole Alkaloids from Inadequately Dried Leaves of Alstonia scholaris

Six new indole alkaloids,named alstoniascholarines L–Q(1–6),together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris.Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values.In addition,the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.

Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. in Mice and Rats

Alstonia scholaris(L.)R.Br.(Apocynaceae)is an evergreen tree that has been used to treat lung diseases.In this study,the toxicity profile of indole alkaloids from leaves of A.scholaris was investigated.In acute toxicity tests,mice were adminis-tered total alkaloids(TA)and five indole alkaloids.In a chronic toxicity test,rats were continuously administered TA(50,100,and 300 mg/kg bw)for 13 weeks,followed by a 4-week recovery.A single administration of TA affected the behavior of mice,and at 12.8 g/kg bw,prone position,shortness of breath,wheezing,and convulsion were observed.The half-lethal dose(LD50)in mice was 5.48 g/kg bw,almost 2740 times the clinical dose in humans.Among the five indole alkaloids,the maximum tolerance dose in mice ranged from 0.75 to 4 g/kg bw.The TA-treated rats did not die and showed no adverse effects or dose-dependent changes in weight or food and water consumption,despite fluctuations in hematological and bio-chemical parameters compared with historical data.Furthermore,both gross and histopathological observations revealed no abnormalities in any organ.With daily oral administration to rats,the non-observed-adverse-effect-level of TA was 100 mg/kg bw.The results indicate that TA is safe for clinical use.

Genotoxicity and Safety Pharmacology Studies of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br.

Indole alkaloids extract(IAAS)was prepared from leaves of Alstonia scholaris(L.)R.Br.,an evergreen tropical plant widely distributed throughout the world.This plant has been used historically by the Dai ethnic people of China to treat respiratory diseases.This study evaluated the genotoxicity and safety pharmacology of IAAS to support clinical use.The bacterial reverse mutation(Ames)test,in vitro mammalian chromosomal aberration test,and in vivo mammalian erythrocyte micronucleus(MN)test were performed to evaluate genotoxicity.Mice were administered IAAS(240,480,or 960 mg/kg bw)once orally to observe adverse central nervous system effects.Furthermore,beagle dogs were administered IAAS(10,30,60 mg/kg bw)once via the duodenum to evaluate its effects on the cardiovascular and respiratory systems.IAAS with or without S9-induced metabolic activation showed no genotoxicity in the Ames test up to 500μg/plate,in the mammalian chromosomal aberration test up to 710μg/mL,or in the MN test up to 800 mg/kg bw.No abnormal neurobehavioral effects were observed in mice following treatment with up to 960 mg/kg bw of IAAS.Moreover,blood pressure,heart rate,electrocardiogram parameters,and depth and rate of breathing in anesthetized beagle dogs did not differ among the IAAS doses or from the vehicle group.These data indicated that IAAS did not induce mutagenicity,clastogenicity,or genotoxicity,and no pharmaco-toxicological effects were observed in the respiratory,cardiovascular,or central nervous systems.Our results increased understanding of safety considerations associated with IAAS,and may indicate that IAAS is a possible drug candidate.

Anti-microbial Effects In Vitro and In Vivo of Alstonia scholaris

Alstonia scholaris could be used as a traditional medicinal plant in China for the treatment of acute respiratory,which might be caused by respiratory tract infections.The investigation tested the anti-infective effects of total alkaloids extract(TA)from leaves of A.scholaris,and as a result,TA inhibited herpes simplex virus type 1(HSV-1),respiratory syncytial virus(RSV)and influenza A virus(H1N1)in vitro respectively.In addition,the survival days of mice were prolonged,and the lung weights and mortality of mice were decreased significantly,after oral administrated TA in H1N1 and beta-hemolytic streptococcus infectious models in vivo respectively.The finding supported partly the traditional usage of A.scholaris in the treatment of respiratory infections.

Four new corynanthe-type alkaloids from the roots of Alstonia scholaris

Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.