Phytochemical Composition, Anti-psoriatic Activity, and Safety Evaluation of the Ethanolic Extract of Iraqi Anagyris foetida L. Leaves

Acute and subacute toxicity studies of Lygodium flexuosum extracts in rats

Background: Ajania purpurea. C. Shih commonly used in traditional Tibetan medicine. It is known for its therapeutic effects on conditions like lung heat, pharyngitis, and thoracic empyema. Toxicity evaluation includes acute toxicity test, subacute toxicity test, subchronic toxicity test, reproductive and developmental toxicity test, etc. Toxicity test is one of the important indicators to determine its safety.Methods: To assess the acute and subacute toxicity of ethanol extract from A. Prpurea.whole plant (EAP), both mice and rats were used to conduct acute and subacute toxicity experiments. Mice were administered a one-time dose of A. purpurea ethanol extract at 2000 mg/kg in acute toxicity study. In subacute toxicity experiments, doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg were administered for 28 consecutive days. The behavior, body weight, organ coefficient, complete blood cell count, blood biochemistry and histopathological section were observed.Results: In the subacute toxicity experiment, SD rats were orally administered A. Prpurea. ethanol extract for a continuous period of 28 days at doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg respectively. The animals' behavior, body weight, organ coefficients, blood biochemical parameters, complete blood count and histopathological changes were observed. The results showed that compared to the control group, the rats treated with 400 mg/kg and 800 mg/kg of Ajania purpurea.C. Shih extract exhibited highly significant differences in blood biochemical liver function, and noticeable pathological changes in organ tissues.Disscussion: Based on the overall experimental results, this study found that A. Prpurea. exhibited no toxicity in terms of acute toxicity.

P9 The effect of ethanolic extract of red betel vine leaves (Piper crocatum) to the livers and kidneys of DDY mice in acute and subchronic toxicity study

The aim of the study was to evaluate the acute oral and sub-acute toxicity of ethanolic root extract of Tetracera akara in Swiss albino mice and Wistar rats. Tetracera akara (Burm. f.) Merr. has been used as traditional medicine by the Kani tribe of Kerala to cure liver diseases. In acute toxicity studies, four groups of mice (n = 5/group/sex) were orally treated with doses of 0.625 g, 1.25 g, 2.5 g and 5.0 g/kg and mortality were recorded. In the sub-acute toxicity study, animals received T. akara extract at the doses of 0.1 g, 0.5 g and 2.5 g/kg/day (n = 5/group/sex) for 28 days, biochemical, hematological, morphological and histopathological parameters were determined. T. akara did not produce any mortality in the acute toxicity studies, showing LD50 higher than 5 g/kg. Sub-acute treatment with T. akara didn’t cause any changes in body weight gain, hematological, biochemical profiles when compared to normal control. In addition, no changes in morphological and histopathological aspect of organs were observed in the animals. Taking all factors into consideration, administration of Tetracera akara does not produce acute toxicity in Swiss albino mice or sub-acute toxicity in Wistar rats, suggesting it’s safe use by humans.

The aim of the study was to evaluate the acute and sub-acute toxicity of ethanolic root extract of Tetracera akara in Swiss albino mice and Wistar rats. Tetracera akara (Burm. f.) Merr. has been used as traditional medicine by the Kani tribe of Kerala to cure liver diseases. In acute toxicity studies, four groups of mice (n = 5/group/sex) were orally treated with doses of 0.625 g, 1.25 g, 2.5 g and 5.0 g/kg and mortality were recorded. In the subacute toxicity study, animals received T. akara extract at the doses of 0.1 g, 0.5 g and 2.5 g/kg/day (n = 5/group/sex) for 28 days and biochemical, hematological, morphological and histopathological parameters were determined. T. akara did not produce any mortality in the acute toxicity studies, showing LD50 higher than 5 g/kg. Sub-acute treatment with T. akara didn’t cause any changes in body weight gain, hematological, biochemical profiles when compared to normal control. In addition, no changes in morphological and histopathological aspect of organs were observed in the animals. Taking all factors into consideration, administration of Tetracera akara does not produce acute toxicity in Swiss albino mice and sub-acute toxicity in Wistar rats, suggesting it’s safe use by humans.

A novel pleuromutilin derivative, compound 4g with a cyclobutyl side chain, was identified and found to have good antibacterial activity, including methicillin-resistant Staphylococcus aureus (MRSA) and Mycoplasma. In order to evaluate its safety profile, acute and 28-day oral toxicity studies were carried out. An acute toxicity study in rats revealed that the oral LD50 of 4g exceeded 5000 mg/kg, indicating that the compound had low acute toxicity. In a 28-day oral toxicity test, the rats were repeatedly administered 0, 300, 1000, and 3000 mg/kg doses and showed no adverse clinical symptoms or death. Although 4g did not affect body weight, hematological findings indicated dose-dependent inflammatory changes at 1000 and 3000 mg/kg. Serum biochemistry showed decreases in alanine aminotransferase (ALT) and alkaline phosphatase (ALP), suggesting adaptive metabolic responses rather than classic hepatocellular injury. Significantly, dose-dependent increases in relative liver weight were observed at all dose levels, accompanied by minimal hepatocyte steatosis and altered serum lipid profiles, identifying the liver as a primary target organ. Based on the totality of findings, the no-observed-adverse-effect level (NOAEL) was determined to be 300 mg/kg. In conclusion, pleuromutilin derivative 4g has low toxicity, which provides the theoretical basis to further investigate for a new candidate drug.

Thai herbal formulation ‘Ya-Pit-Samut-Noi’: Its antibacterial activities, effects on bacterial virulence factors and in vivo acute toxicity

The objective of this work was to evaluate the antiplasmodial activity and toxicity of the extract and fractions obtained from the bark of Aspidosperma nitidum. The ethanol extract obtained from the powdered bark of plants was acid-base partitioned and phytochemically analyzed. The antiplasmodial activity, in vivo antimalarial activity and in vitro cytotoxicity were acessed. The selectivity index (SI) was calculated. The acute oral toxicity and pathological effects, of the ethanol extract was evaluated in mice. The major constituent of the ethanol extract was suggestive of a β-carboline chromophore. The alkaloid and neutral fractions contained compounds with an aspidospermine core as the major constituent. The ethanol extract (IC50 = 3.60 µg/mL), neutral fraction (IC50 = 3.34 µg/mL) and alkaloid fraction (IC50= 2.32 µg/mL) showed high activity against P. falciparum (W2 strain). The ethanol extract and the alkaloid fraction reduced 80% of the parasitemia of P. berghei (ANKA)-infected mice (dose of 500 mg/kg) in the 5th day, which was not sustainable at the 8th day. A similar result was obtained for chloroquine. The ethanol extract (CC50 = 410.65 µg/mL; SI = 114.07), neutral fraction (CC50 = 452.53 µg/mL; SI = 135.49), and alkaloid fraction (CC50 =346.73 µg/mL; SI 149.45) demonstrated low cytotoxicity and high SI. The ethanol extract (5000 mg/kg; gavage) presented low acute oral toxicity, with no clinical or anatomopathological modifications being observed (in comparison to the control group). In vitro studies with a chloroquine-resistant clone of P. falciparum confirmed the antiplasmodial activity of the A. nitidum ethanol extract, and its fractions had low cytotoxicity for HepG2 cells. In vivo studies with P. berghei–infected mice and acute toxicity studies corroborated these results.

The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one ton per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e., NO(A)EL at or above the limit test threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e., LD50 above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD50. According to the REACH Regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline, in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral toxicity study by using this adaptation.

The use of crude herbal decoctions in the traditional treatment of diseases is a common practice. Pogostemon benghalensis and P. cablin are commonly used for treatment of diverse categories of diseases such as infectious and non-infectious disease. Native people use the crude decoctions as bactericidal, antimalarial, anti-leshimania, anti-diarrheal and insecticidal activities. Its safety profile is not yet elucidated and therefore, this study was to analyze the acute toxicity of essential oils (Eos) from P. benghalensis and P. cablin as medicinal. Methods include acute toxicity study using male and female Wistar albino rats with single oral dose and followed up to 14 days as per the guidelines of OECD. Visual observations were carried regularly during the experimental period while body weight was measured weekly. Organ weight, clinical chemistry and hematology data were collected on the 7th and 14th days. Results were presented as mean ± standard deviation. One-way analysis of variance (ANOVA) was carried. Oral administration of Eos from P. benghalensis and P. cablin revealed no treatment-related mortality in female rats up to the dose of 5000 mg/kg. In acute toxicity studies, no remarkable treatment related anomalies were observed compared to negative controls. Food consumption, body weight, organ weight, hematology did not showed sound variation between controls and treatment groups. However, creatinine, triglycerides, and monocytes were lower in the treated groups in 7th day as compared to control groups. No significant variations between male and female groups in relative organ weight, hematology were noticed. In conclusion, the Eos from P. benghalensis and P. cablin showed LD50 > 3000 mg/kg in acute toxicity studies.
 Keywords: Pogostemon benghalensis, P. cablin, traditional medicine, safety, plant medicine, adverse effect, acute oral toxicity

Background/Objectives: Mucuna pruriens (Linn.) DC. var. pruriens is a leguminous plant whose seeds have been used in traditional medicine, including for the enhancement of sexual function. However, scientific evidence regarding its toxicological safety remains limited. Accordingly, the present study aimed to investigate the acute and chronic oral toxicity of the ethanolic seed extract of M. pruriens var. pruriens in Sprague-Dawley rats. Methods: Acute oral toxicity was assessed in female rats following a single oral administration of the ethanolic seed extract of M. pruriens var. pruriens at a dose of 5000 mg/kg body weight, with animals monitored for general behavior, clinical signs, and mortality over a 14-day period. Chronic oral toxicity was evaluated in female and male rats administered the ethanolic seed extract of M. pruriens var. pruriens at doses of 100, 500, and 2500 mg/kg body weight daily for 270 days. Animals were monitored for general behavior, clinical signs, and health status throughout the study. Hematological, blood chemistry, gross pathological, and histopathological assessments were conducted at study termination. Results: In the acute oral toxicity study, no mortality or treatment-related behavioral abnormalities or clinical signs were observed in female rats receiving the ethanolic seed extract of M. pruriens var. pruriens, and findings were comparable to those of the control group. In the chronic oral toxicity study, no mortality occurred in any treatment group. Although statistically significant increases or decreases were observed in certain body weight, organ weight, hematological, and blood biochemical parameters compared with the control group, all values remained within established reference ranges. When considered together with the absence of abnormal behavioral changes, clinical signs, and gross pathological or histopathological alterations in major organs, these findings indicate that long-term oral administration of the ethanolic seed extract of M. pruriens var. pruriens did not result in chronic toxicity. Conclusions: The ethanolic seed extract of M. pruriens var. pruriens did not produce acute or chronic oral toxicity in Sprague-Dawley rats. Nevertheless, further clinical investigations are recommended to confirm its long-term safety for human use.

Introduction:Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. No drug has been generally approved as safe and effective for the treatment of COVID-19. Several therapeutic agents such as COVID Organics® (CVO) have been explored as treatment options. CVO is an herbal tea composed of 62% of Artemisia annua and 38% of other plants. There is presently no existing scientific report and data on the safety and efficacy of CVO herbal drug. Thus, acute and subacute toxicity studies were undertaken to evaluate the safety and toxicity of CVO on short- and long-term usage in animal models.Materials and Methods:Phytochemical and nutritional compositions of CVO were determined using standard methods. Acute oral toxicity was investigated using female Swiss albino mice (three per group). While subacute oral toxicity was done using female and male Swiss albino rats (five per group). The animals were administered 2000 mg/kg, 5000 mg/kg, therapeutic dose; 5500 mg/kg and supratherapeutic dose; 11,000 mg/kg of CVO herbal product. The control group received water ad libitum. The oral toxicity studies were done in accordance with Organization for Economic Corporation and Development guidelines. The experimental protocol was approved by the Institutional Animal Care and Use Committee, Nigerian Institute of Medical Research (Ethics No. IRB/17/043).Results:CVO is rich in antioxidants: flavonoids (10.3%), tannins (29.1%), and phenolics (434.4 mg). It contains proteins (33.8%), carbohydrates (34.5%), fat (6.8%), and fiber (0.5%). In the acute toxicity study, no mortality was recorded in all the treated and untreated groups. The lethal dose of CVO is >5000 mg/kg body weight. The hematological, biochemical, lipid profile, and histologic parameters were all normal at therapeutic doses when compared to the control group.Conclusion:The acute and subacute oral toxicity studies revealed that CVO is not toxic. The specific organ toxicity evaluations also indicated that CVO has no toxic effects on blood parameters and vital organs structure and function at therapeutic dose. Thus, CVO is safe for short- and long-term usage. We recommend that CVO should be subjected to efficacy studies to investigate whether it is effective for COVID-19 treatment as claimed by the manufacturer.

Comprehensive phytochemical characterization, antioxidant potency, and toxicological evaluation of Paederia foetida in Wistar albino rats: Insights into therapeutic efficacy and safety profiles.

Over 80% of cultural societies in low-income countries use plant preparations in traditional medicine with unknown potency and safety profiles. Uvariodendron anisatum root extracts are used by some Kenyan herbalists. However, the claims of the plant to remove retained placenta during birth have remained uninvestigated. Therefore, the current study evaluated its uterotonic activities. Acute toxicity in Wistar rats and the phytochemical composition of the plant were also studied. The plant was collected from Embu County in Kenya. The water and ethanol extracts were prepared by maceration. Uterine strips were isolated from primed mature female Wistar rats and used to study the uterotonic activities of the extracts. De Jalon's solution and oxytocin were used as negative and positive controls, respectively. Acute oral toxicity studies were done following the OECD 423 guideline and phytochemical screening were based on standard phytochemical procedures. The study met all the approval requirements before commencement. Data obtained from the uterotonic activity were analysed by using GraphPad Prism Version 8.0.1 software and expressed as a percentage increase or decrease of mean as mean ± SEM relative to the controls. The findings of acute oral toxicity were expressed using LD50. Additionally, the phytochemical components of the U. anisatum were tabulated. The uterotonic effect of Uvariodendron anisatum root water extract was higher than that of ethanol extract. A single dose of the Uvariodendron anisatum root water extract at 2000 mg/kg did not cause mortality in the tested Wistar rats. Besides, there were no changes in hematological and biochemical parameters. The extracts did not reveal changes in the gross morphology of the liver, kidney, heart, and lung of the tested Wistar rats. However, the histopathological studies of Uvariodendron anisatum root water extracts exhibited toxicity in the liver, kidney, and lung tissues of Wistar rats at a concentration of 2000 mg/kg. Alkaloids, glycosides, saponins, phytosterols, terpenes, proteins, phenols, and oils were recorded in Uvariodendron anisatum. The findings from this study provided scientific evidence which is useful in validating the use of Uvariodendron anisatum extracts in the stimulation of the uterus during birth.

Introduction: Kadukkai chooranam is an effective drug composition from siddha medicine used for the management of Menorrhagia/Dysfunctional Uterine bleeding (Pitha perumbaadu) which is referenced from a classical age-old text Agathiyar attavanai vaagadam. Aim of this study The aim of study was to assess the acute and sub-acute toxicity of the polyherbal composition kadukkai chooranam. Methodology: In the acute toxicity study, a single dose of 2000 mg/kg was administered to wistar albino female rat (200-220g) after the proper acclimatization and fasting procedures was made as per the OECD 423 – acute toxicity guidelines. All the animals were observed for physical symptoms and behavioral changes for first 72 h. In sub-acute toxicity study repeated doses of the polyherbal composition was administered to Wistar albino rats of both genders, separately acclimatized for 7 days and fasted as per OECD -407 guidelines. The animals received two doses of drug (100 mg/kg/day and 200 mg/kg/day) for a period of 28 days. On 28th day of experiment, blood sampling of animals was done for hematological and biochemical analysis i.e. liver and renal function parameters, lipid profile and then sacrificed for histopathological study of liver and kidney. The rats were observed daily during the period of study, and sacrificed on the 29th day. Observation parameters of the animals included a comparative evaluation of general appearance/behaviour, morbidity/mortality, body weights, haematology, biochemistry, lipid profile and histopathology of major organs of treated and control groups. Results There was no morbidity and mortality noticed with single dose administration in acute toxicity study in wistar rats. In sub-acute toxicity study, no morphological changes were observed in kidney, liver and spleen of animals at dose of 100 mg/kg/day and 200 mg/kg/day. Conclusions The results of the present study show that oral administration of kadukkai chooranam did not produce any severe toxic effects in both acute and sub-acute studies in Wistar rats. Therefore, usage of an appropriate dosage will be preferable and considered as safe.