Acute and Sub-acute Oral Toxicity Assessment of a Standardized Polyherbal Preparation POL-6 in Rats

Background: A standardized polyherbal preparation (POL-6) containing six plant extracts Hypericum perforatum, Bacopa monnieri, Centella asiatica, Withania somnifera, Ocimum sanctum and Camellia sinesis have good antioxidant, anti-inflammatory, and immunomodulatory activities. The present study was carried out to evaluate the safety profile of POL-6 through acute and subacute oral toxicity models in Wistar rats. Methods: In acute safety evaluation, a single dose of 2000mg/kg of POL-6 was given orally to five rats and was observed for 14 days. In subacute safety evaluation POL-6 at the doses of 250, 500 and 1000 mg/kg was given orally to the rats once a day for 28 days. The animals were observed for the signs of toxicity and mortality during the study period. Results: In acute toxicity evaluation, POL-6 treatment did not show any toxic signs and mortality in animals during the observation period. In subacute toxicity studies, no changes were seen in any of the dose levels of POL-6 treatment during the total body weights, organ weights and hematobiochemical parameters examination of the rats. No lesions were seen during the gross/histopathological examination. Conclusion: The study revealed that administration of POL-6 for 28 days showed no significant treatment generated toxic effects in the animals, hence it can be considered as non-toxic if it is ingested in a time not greater than a month.

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A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats

INQUIRY The Journal of Health Care Organization Provision and Financing ◽

10.1177/00469580211056044 ◽

2021 ◽

Vol 58 ◽

pp. 004695802110560

Author(s):

Min Hong ◽

Min Lu ◽

Yimin Qian ◽

Liping Wei ◽

Yaqun Zhang ◽

...

Keyword(s):

Clinical Chemistry ◽

Recovery Period ◽

Safety Evaluation ◽

Toxicity Assessment ◽

Sprague Dawley ◽

Oral Toxicity ◽

Renal Tubular Cells ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Renal Tubular

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

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Safety assessment of essential oils from Xylopia aethiopica (Dunal) fruit from Nigeria

Biomedical Research and Therapy ◽

10.15419/bmrat.v7i7.616 ◽

2020 ◽

Vol 7 (7) ◽

pp. 3865-3876

Author(s):

Raphael Chukwuma Ekeanyanwu ◽

Nnaemeka Emmanuel Mgbedo ◽

Alvan Tochukwu Njoku

Keyword(s):

Essential Oils ◽

Histopathological Examination ◽

Initial Period ◽

Safety Evaluation ◽

Toxicity Tests ◽

High Dose ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

High Dose Level ◽

Xylopia Aethiopica

Introduction: The essential oils of Xylopia aethiopica fruits have been reported to possess numerous biochemical effects. However, no toxicological data is available regarding the safety evaluation of the essential oils from the plant spice. The present study was performed to evaluate the safety of essential oils from X. aethiopica (XAEO) fruit by acute and sub-acute oral toxicity studies in experimental rodents. Methods: In assessing the safety of XAEO, acute and sub-acute oral toxicity tests were performed following OECD guidelines 425 and 407, respectively, with slight modifications. At the end of each test, hematological and biochemical analysis of the collected blood was performed. Histopathological examination of vital organs of the animals was conducted for gross findings and for comparison to controls. Results: In acute oral toxicity, signs of toxicity were observed in the initial period of the experiment which culminated in the death of the mice before the end of the experiment. The sub-acute test observations indicated that generally, there were no significant differences (p<0.05) up to the high dose level compared to the controls. Conclusion: This study demonstrated the tolerability of XAEO administered daily for 28 days up to 450 mg/kg dose.

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Safety Evaluation ofYukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/672136 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Hyekyung Ha ◽

Jun Kyoung Lee ◽

Ho Young Lee ◽

Woo Suk Koh ◽

Chang Seob Seo ◽

...

Keyword(s):

Body Weight ◽

Single Dose ◽

Safety Information ◽

Clinical Signs ◽

Safety Evaluation ◽

Sprague Dawley ◽

Weight Changes ◽

Oral Toxicity ◽

Renal Disorder ◽

Body Weights

Yukmijihwang-tang(YMJ;Liu wei di huang tang(China),Rokumigan(Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day.

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Safety evaluation on defatted soybean particles after nanofabrication

Quality Assurance and Safety of Crops & Foods ◽

10.15586/qas.v12i3.760 ◽

2020 ◽

Vol 12 (3) ◽

pp. 87-101

Author(s):

Shenguang Tong ◽

Hongjiang Hao ◽

Xiaofei Li ◽

Hongbo Li ◽

Zhiyong Liao ◽

...

Keyword(s):

Cell Proliferation ◽

Particle Size ◽

Body Weight ◽

Single Dose ◽

Histopathological Examination ◽

Safety Evaluation ◽

Inflammatory Lesion ◽

Toxicity Assessment ◽

Abnormal Behavior ◽

Traditional Food

Many nanoparticles are used in food for increasing the bioavailability of nutrients. Nano defatted soybean particles (nDSPs) were promising as nanoparticles of a traditional food, but its safety remains pending. In this work, the possible toxicity of nDSP was tested on cell and mouse models. Cell proliferation and the viability of defatted soybean particles (DSPs), DSP tracking in gastrointestinal, and tissue histopathological examination were performed. The Zeta potential of nDSP was as low as ?16 ± 3 mV and had no cytotoxicity on Caco-2 cells or animal models. In the gastrointestinal tract, the nDSP showed similar absorption patterns with DSP of 500 nm or 1 ?m. In acute toxicity assessment, no abnormal behavior was observed in mice after DSP administration, and no noticeable tissue damage and inflammatory lesion were found either. Here, we show that DSPs, including nDSP, are safe at a single dose of 10 g/kg body weight, regardless of the particle size. The food property and aggregation behavior both help to make the nanoparticle safe.

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A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03181-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lalit Sharma ◽

Aditi Sharma ◽

Ashutosh Kumar Dash ◽

Gopal Singh Bisht ◽

Girdhari Lal Gupta

Keyword(s):

Gene Expression ◽

Alcohol Withdrawal ◽

Therapeutic Potential ◽

Centella Asiatica ◽

Ethanol Withdrawal ◽

In Vivo Studies ◽

Ocimum Sanctum ◽

Behavioral Parameters ◽

Gene Expression Studies

Abstract Background Alcohol abuse is a major problem worldwide and it affects people’s health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6–24 h after the last alcohol ingestion. Methods The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals’ free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABAA receptor subunits in the amygdala and hippocampus. Results Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats. Conclusion The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.

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Acute and subacute toxicity assessment of Madhulai Manappagu (Siddha herbal syrup formulation) in animal model

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2020-0327 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Meenakshi Sundaram Malayappan ◽

Gayathri Natarajan ◽

Logamanian Mockaiyathevar ◽

Meenakumari Ramasamy

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Route ◽

Toxicity Assessment ◽

Toxicity Study ◽

Female Rats ◽

Albino Rats ◽

Oral Toxicity ◽

Gross Pathology ◽

Toxicity Studies

Abstract Objectives Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats. Methods The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses. Conclusions The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.

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