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

ABSTRACT: 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 500 ?g/plate, in the mammalian chromosomal aberration test up to 710 ?g/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.

SUBMITTER: Zhao YL

PROVIDER: S-EPMC7253540 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Zhao Yun-Li YL Su Min M Shang Jian-Hua JH Wang Xia X Bao Guang-Lei GL Ma Jia J Sun Qing-Di QD Yuan Fang F Wang Jing-Kun JK Luo Xiao-Dong XD

Natural products and bioprospecting 20200430 3

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 (M ...[more]

PMID: 32356224

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Project description:ObjectivesThe primary symptoms associated with snake envenomation are both systemic and local. The local symptoms are characterized by pain, swelling, haemorrhage and myonecrosis at the site of bite. The present study investigates the ameliorating effect of the aqueous bark extract of Alstonia scholaris bark on viper venom induced histopathological and biochemical changes in liver and kidney of swiss albino mice models.Methods & materialsSwiss albino mice (20?±?2)g were treated with sublethal doses(0.5??g and 1??g) of Vipera russelli venom(VRV) intraperitonially The following groups were assigned in the study-Group I(saline control); Group II & III(Venom treated-0.5??g ie ¼ LD50 and 1??g ie 1/2 LD50) and Group IV &V(Venom-0.5??g and 1??g respectively incubated with Aqueous Alstonia scholaris (AAS) extract; 200?mg/kg bw) and Group VI (Antivenom serum (AVS) (2?mg/ml) followed by 1??g Vipera russelli venom (VRV). The animals were sacrificed and their organs were immersed in Bouin's fixative for 24?h and stained with haematoxylin/eosin and observed under the microscope. The serum samples were collected from the animals and tested for serum Alanine transaminase (ALT) and Aspartate transaminases (AST) following the method of Reitman & Frankel(1957) and serum creatinine.ResultsThe histological alterations observed in Group II and III liver sections were mainly pyknosis, karyorrhexis, cytoplasmic vacuolation, necrosis, fatty changes and hepatocytes atrophy. Sinusoidal dilatation, amyloidosis, portal vein thrombosis which was significantly reduced by AAS extract in Groups IV and V. A venom dose of 1??g induced tubular cell acidophilia indicating cell damage, peritubular congestion, degenerating changes in the proximal tubules in the form of cytoplasmic vacuolations, partially destroyed bowman's capillaries with dilated Bowman's space in Group III that was significantly reduced by Aqueous Alstonia scholaris (AAS) (200?mg/kg bw) extract in Groups IV and Group V.AVS gave significant protection against venom induced action in Group VI.ConclusionThe present paper thus highlights the histopathological changes associated with Vipera russelli venom and systemic venom neutralization potential of Aqueous Alstonia scholaris (AAS) in animal models.

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

Publications

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

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