Acute Oral Toxicity Study Research Articles

Evaluation of acute, 28-day, 13-week repeated dose oral toxicity and genotoxicity of a herbal extract (HemoHIM G) from Angelica sinensis, Ligusticum chuanxiong, and Peaonia lactiflora.

HemoHIM G is a functional food ingredient composed of a triple herbal combination of Angelica sinensis, Ligusticum chuanxiong, and Paeonia lactiflora, to improve impaired immune function. Considering the pharmacological benefits of its constituent herbal components, HemoHIM G is anticipated to have various health benefits; however, its toxicity has not been thoroughly evaluated. Here, we conducted a comprehensive study to assess the safety of HemoHIM G in terms of acute oral toxicity, 13-week repeat-dose toxicity, and genotoxicity. In the oral acute toxicity study, Sprague-Dawley rats were orally administered a single dose of HemoHIM G at 5000mg/kg/day, the limit dose for the acute study. No abnormal findings or adverse effects were observed in this study, as confirmed by gross pathology. A 13-week repeated-dose toxicity study was conducted with HemoHIM G at doses of 1250, 2500, and 5000mg/kg/day to examine the subchronic toxicity in both male and female rats after 28days of dose-range finding study. No test substance-related clinical signs or mortality was observed at any of the tested doses. Gross pathology, hematology, blood chemistry, and histopathology were within normal ranges, further supporting the safety of HemoHIM G. Therefore, the NOAEL of HemoHIM G was considered to be at 5000mg/kg/day for both sexes of rats. Bacterial reverse mutation tests, a chromosome aberration test in human peripheral blood lymphocytes, and a mouse micronuclei test were conducted to identify the potential genotoxicity of HemoHIM G. HemoHIM G is non-mutagenic and non-clastogenic. Collectively, these findings provide valuable evidence for the safe use of HemoHIM G as a functional food ingredient.

ACUTE TOXICITY STUDIES OF METHACRYLIC ACID BASED COMPOSITE HYDROGEL OF SALVIA SPINOSA SEED MUCILAGE: A POTENTIAL NON-TOXIC CANDIDATE FOR DRUG DELIVERY

Safety evaluation of a newly designed polymeric drug delivery system (DDS), with/without the addition of active pharmaceutical ingredients (APIs), is now mandatory for their regulatory approval for human use. Hence, Salvia spinosa seed mucilage/hydrogel (SSH) was treated with methacrylic acid (MAA) to synthesize a composite hydrogel (SSH-co-MAA). Acute oral and acute dermal toxicity studies of the SSH-co-MAA for API delivery were ascertained following OECD guidelines 420 and 402, respectively. Moreover, an ocular toxicity study was also performed and analyzed through Draize scale. Animals of two species, rodent (rat) and non-rodent (rabbit), were divided into four groups. Group A of both rats and rabbits was assigned as control and remained untreated. Meanwhile, groups B, C, and D were labelled as treated groups and received a single dose of SSH-co-MAA, i.e., 0.05, 0.3 and 2 g/kg body weight of the animal. During 14 days after the treatment, animal monitoring was done for behavioral changes, food and water intake, adverse effects, and mortality. All animals remained alive, with no statistically significant abnormality. Hematological and biochemical parameters of control and treated animals were analyzed after the completion of 14 days and found in harmonization. The vital organs of rats were removed to determine absolute organ weights. Histopathology of the vital organs of rats revealed normal cellular architecture, without any lesions. SSH-co-MAA was also free from dermal and ocular toxicity. The overall results of acute oral and dermal toxicity studies prove that SSH-co-MAA is safe, especially after oral administration. Hence, SSH-co-MAA can be used as a non-toxic excipient for drug delivery systems.

Integration of transcriptomics and metabolomics reveals toxicological mechanisms of ZhuRiHeng drop pill in the 180-day repeated oral toxicity study.

Background: ZhuRiHeng Drop Pill (ZRH) is a traditional Mongolian medicinal preparation. Despite its long history of use for the treatment of coronary heart disease, there have been few toxicological studies of the safety profile of ZRH. Purpose: In order to comprehensively elucidate the underlying mechanisms behind the observed toxicity of ZRH on rat livers in the 180-day repeated oral toxicity study, we conducted a comprehensive analysis by integrating transcriptomic and metabolomic data. Methods: High-resolution mass spectrometry was conducted to evaluate the constituents of ZRH. For the acute oral toxicity study, mice were administered a dose of 32g/(kg·d) of ZRH, while rats were instead orally administered 0.934, 1.868, or 3.736g/(kg·d) of ZRH over a 180-day period in a 180-day repeated oral toxicity study. Conventional index and organ weights/histology were then monitored to detect any potential ZRH treatment-related toxicity. To identify key genes and metabolites involved in ZRH toxicological processes, we performed transcriptomic and metabolomic analyses of liver tissue upon ZRH treatment using RNA-seq techniques, qPCR and liquid chromatography-mass spectrometry analyses. Results: A total of 60 compounds in ZRH were identified and speculated in positive and negative ion modes. Mice in the acute toxicity study exhibited no signs of ZRH-related toxicity. In a protracted oral toxicity investigation spanning 180 days, discernible elevations in liver ratios were noted in both male and female rats across all three dose cohorts, relative to the control group (p < 0.05 or p < 0.01). Upon subjecting to ZRH treatment, our transcriptomic and qPCR analyses unveiled notable upregulation of crucial genes, exemplified by Abcb1b and Cyp2b2, known for theirs involvement in liver drug transport and metabolism function. Furthermore, our untargeted metabolomic analysis provided supplementary insights, revealing significant regulation in pyrimidine metabolism, as well as alanine, aspartate, and glutamate metabolism pathways. Conclusion: Our study unveils a panoramic understanding of the temporal, dosage-specific, and gene dimensions surrounding the metabolic and transcriptional shifts induced by ZRH exposure. As we peer into the future, recommendations emerge for further exploration, encompassing aspects such as time dynamics, dosage considerations, and gene-centric avenues to enhance therapeutic efficacy.

Novel insulin-montmorillonite sodium complex containing pH regulated nanocomposite hydrogels

Main objective of current work was to develop pH responsive polymeric systems for safe oral delivery of insulin. A novel fenugreek seed mucilage extract-based pH-regulated hydrogel (FA) system by free radical polymerization. Insulin was directly post-loaded in developed hydrogels (I-FA) as well as in the form of insulin-montmorillonite-Na + complexes (I-MT) to prepare nanocomposite (NC) hydrogels (I-MT-FA). Both I-FA and I-MT-FA NC hydrogels were subjected to FTIR, PXRD, EDX, SEM, DSC, and TGA studies. FTIR, PXRD, and EDX results validated the safe incorporation of insulin in both formulation types. SEM photomicrographs showed variable surface morphology. Thermal studies ensured the higher thermal stability of I-MT-FA NC hydrogels. Gel fraction (%) analysis, swelling studies (%), and in-vitro release studies (%) were also performed. In-vivo pharmacodynamics and pharmacokinetics evaluations of the two optimized formulations (I-FA6 hydrogel and I-MT-FA6 NC hydrogel) showed relative bioavailability of 26.15 times for I-FA hydrogel and 50.65 times for I-MT-FA6 NC hydrogels against oral insulin solution. Acute oral toxicity studies ensured the safety and biocompatibility of developed networks among research animals.

Synergistic Antibacterial Activity of Gallic Acid Based Chalcone Indl 2 by Inhibiting Efflux Pump Transporters.

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps.

Acute Oral Toxicity, Antioxidant Activity and Molecular Docking Study of 2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4-chlorophenyl)-3-cyano-4H-chromen- 2-yl]-acetamide.

Several studies have been conducted on 4-H chromene compounds because of their intriguing pharmacological and biological properties. Various new natural compounds having a chromene foundation have been reported over the past 20 years. In the present study, we reported the acute oral toxicity, antioxidant activity, and molecular docking study of the most active 4H-chromene derivative2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4- chlorophenyl)-3-cyano-4H-chromen-2-yl]-acetamide (A9). The acute oral toxicity was carried out as per OECD 423 guidelines. For investigating the antioxidant activity, various biochemical parameters in colon tissue like SOD, CAT, MDA, PC and GSH and also enzyme levels, such as ALT, AST, ALP, and LDH, were measured in this experiment. Acute oral toxicity study indicated that the A9 ligand was found to be safer in animals. Additionally, the A9 ligand had significant antioxidant properties at various doses and was not found to be harmful to the liver. Due to its stronger binding energy and the appropriate interactions that induce inhibition, the A9 ligand's antioxidant function was also validated by additional molecular docking research. This compound can be exploited as a lead molecule in further research.

Oral Safety Evaluation of the Aqueous Fruit Extract of Annona Muricata in Wistar Rats

Annona muricata fruit (i.e. Soursoup or custard apple a tropical plant species known for its edible fruit)has been attributed with numerous medicinal benefits (including antimicrobial, anti-inflammatory, anti-protozoan, antioxidant, anxiolytic, anti-stress, anti-ulcerogenic, wound healing, hepato-protective, anti-icteric, hepatoprotective, anticancer and antihyperglycemic activities) as well as some toxicological effects (neurotoxicity and neurodegeneration). Despite its ancestral use and wide applications in human health, scientific information on its oral safety remains scanty. In this study, the oral safety of 100 mg/kd/day, 200 mg/kg/day and 400 mg/kg/day of the aqueous fruit extract of Annona Muricata (AFAM) was evaluated in young adult, male and female white albino Wistar rats using standard acute and 42-days sub-chronic oral toxicity testing guidelines on anthropometric, biochemical, hematological and histo-pathological endpoints. In addition, preliminary qualitative and quantitative analyses of AFAM were undertaken using standard procedures. Results of the study showed that the estimated LD50 value for the acute oral toxicity study of AFAM calculated to be greater than 5 g/kg body weight/oral route although the testing was associated with transient but reversible behavioral toxicities. For its sub-chronic oral toxicity testing, AFAM treatment resulted in profound %weight gain, decreases in the serum triglycerides and very low density lipoprotein cholesterol and liver enzymes. Similarly, prolonged oral AFAM treatments caused significant decrease and increase in the differential neutrophils and platelet counts, respectively while the hist-opathological features of hepatic steatos is and renal tubule collapse in the AFAM-treated livers and kidneys, respectively suggested possible increased intrahepatic lipids biosynthesis and nephrotoxicity. The preliminary phytochemical analyses of AFAM showed the presence and relative amount of flavonoids, alkaloids, tannin, glycosides, saponin, and reducing sugars while the Gas Chromatography-Mass spectroscopy showed the relative abundance of thirteen compounds. Composite analyses conducted on the extract showed the presence of carbohydrate (64.65%), protein (2.14%), moisture content (8.07%), ash value (6.73%), lipid (14.22%) and fiber (4.19%). Overall, the study suggested that the prolonged AFAM oral treatments could predispose to the development of fatty liver disease from de novo intrahepatic biosynthesis of triglycerides, nephrotoxicity and hematotoxicity. In conclusion, the results of this study showed that prolonged consumption of AFAM should be with a great caution as it could pose serious health concerns.

Antipyretic and Antinociceptive Effect of the Methanol Leaf Extract of Ficus asperifolia in Murine Models

Pyrexia occurs as a result of the resetting of the hypothalamic set-point. Non steroidal anti-inflammatory drugs used for the treatment of fever and related illnesses are associated with side effects including gastrointestinal irritation, bleeding, ulcers and perforation. In traditional medicine, many plants have been found to possess antipyretic activity. Ficus asperifolia (Miq), family Moraceae has been traditionally used to treat pain and fevers. The aim of the study was thus to evaluate the antipyretic and antinociceptive activity of the methanol leaf extract of Ficus asperifolia (FME) in murine models. Preliminary phytochemical screening and oral acute toxicity studies were conducted using standard protocols. Antipyretic activity was evaluated using the Brewer’s yeast induced pyrexia model. Antinociceptive effects were investigated using the acetic acid and thermal induced models. The mechanism of action of the plant was also evaluated against several antagonists. FME significantly (p&lt;0.05) and dose dependently reduced yeast induced pyrexia. FME at doses 125, 250 and 500 mg/kg significantly (p&lt;0.05) decreased acetic acid induced abdominal writhes and increased the mean reaction time of mice to thermal-induced pain stimulus. Pre-treatment of mice with naloxone (a non-selective opioid receptor antagonist), glibenclamide (a potassium channel blocker) and L-NNA (a nitric oxide synthase inhibitor) significantly reversed the analgesic action of the extract suggesting that the activity is likely mediated via the involvement of these pathways.

Acute Toxicity Study of Hexane Extract of &lt;i&gt;Sodhita Semecarpus anacardium&lt;/i&gt; L. Drupe in Wistar Albino Rats and its Prediction Using &lt;i&gt;In-Silico&lt;/i&gt; Tool

Semecarpus anacardium L. belongs to the family Anacardiaceae. Its drupe is widely used in Ayurvedic formulations after sodhana processing as it is listed under Schedule E1 of the Drugs and Cosmetics Act 1940. In this study, sodhita Semecarpus anacardium L. drupe was extracted with n-hexane and the yield was found to be 56%. The extract was subjected to GCMS (Gas Chromatography Mass Spectrometry) analysis and its characteristics were studied using an in silico tool. Acute oral and dermal toxicity studies were performed on the Wistar albino rats as per the OECD 425 and 402 guidelines respectively. The GCMS data revealed the presence of C13H18O3 (m/z: 222.1) with an abundance of 93.63%. The compound was predicted as potentially hazardous with a probable mutagenic category of ICH M7 class 3. An oxirane functional group of the compound was predicted to cause potent irritation properties to the eyes and skin with positive scores of 0.76 and 0.57 respectively. The LD50 was found to be more than the limit dose of 2000mg/kg body weight upon oral administration. Acute dermal exposure at a limited dose of 2000mg/kg body weight did not cause mortality. However, inflammatory responses started appearing within 48 hours of exposure. Histopathology revealed mild dermal oedema, mild fibrosis, dilated follicles hyperplasia etc. No changes were found in haematological parameters. Inflammation and dermal allergic reactions were completely self-healed by the end of 14 days. The results suggest that the oil portion of the sodhita drupe possesses the irritant properties of the Semecarpus anacardium. It might be due to the presence of the compound C13H18O3 with Oxirane as a functional group.

Safety assessment of Wuzhuyu decoction extract: acute and subacute oral toxicity studies in rats

Wuzhuyu decoction (WZYD) is a well-known classic traditional Chinese medicine prescription and has been widely used to treat headache, nausea, vomiting, insomnia, etc. However, little published information is available about its safety. Our aim was to investigate the acute and subacute oral toxicity of WZYD extract in rats following the technical guidelines from China’s National Medical Products Administration (NMPA) for single and repeated doses toxicity studies of drugs. Acute oral toxicity was assessed in rats via oral administration of WZYD extract at 4 g/kg three times within a day followed by a 14-day observation period. To evaluate the subacute toxicity, rats were orally administered with WZYD extract at doses of 0, 0.44, 1.33, and 4 g/kg for 28 days. The items examined included clinical signs, body weight, food consumption, hematological and biochemical parameters, bone marrow smear, organ index, and histopathology. After the rats were administered with 12 g/kg (3 × 4 g/kg) WZYD extract, no mortality and toxic effects were observed during the observation period. In the subacute toxicity study, WZYD extract did not cause any significant treatment-related abnormality in each examined item of rats, so the no observed adverse effect level (NOAEL) of WZYD extract for 28 days orally administered to rats is considered to be 4 g/kg, which is approximately 80-fold of its clinical proposed dosage.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida

Ethnopharmacological relevance“Snow-white waterlily” (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. Aim of the studyPolyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. Materials and methodsThe polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. ResultsNCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1β, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. ConclusionThe experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

Qualitative Phytochemical Investigation and Acute Oral Toxicity Study on Ethanolic Extract of Curcuma longa Leaves

The study focused on evaluating the acute toxicity and phytochemical composition of Curcuma longa leaves using Swiss albino mice. The investigation involved a two-phase acute toxicity test, with doses up to 5000 mg/kg administered orally. The results indicated no toxicity at lower doses, while signs of weakness, salivation, and reduced movement were observed at 1600 mg/kg. Lethal effects were noted at 5000 mg/kg, establishing the LD50 at 2154.06 mg/kg. Phytochemical analysis revealed the presence of alkaloids, flavonoids, glycosides, tannins, and volatile oils in the ethanolic extract. The extract exhibited a 27.37% yield, characterized by a yellowish-orange color and a sticky consistency. This comprehensive investigation sheds light on both the acute toxicity profile and the diverse phytochemical components presents in Curcuma longa leaves.&#x0D; Keywords: Curcuma longa, Phytoconstituent, Acute oral toxicity, Lokes method.

ACUTE TOXICITY AND HEPATO-RENAL PROTECTION OF LIME JUICE, HONEY AND THEIR FLAVONOID-RICH FRACTIONS IN HIGH FAT-DIET INDUCED OBESE RAT MODEL

Introduction: A major consideration for the use of alternative herbal medicine from natural compounds is the concern of safety due to possible toxicity. This study evaluated the safety and hepato-renal protection of fresh lime juice (FLJ), raw honey (RH) and their flavonoid-rich fractions in obese rat induced high fat-diet (HFD). Methods: Oral acute toxicity (LD50) study involved 24 female Wistar rats, divided into 8 groups of 3 rats, administered 300 mg/kg and 2000 mg/kg of FLJ, RH, methanol flavonoid rich fraction of lime juice (MFLJ) and ethyl acetate flavonoid rich fraction of honey (EAFH) respectively, for 14 days. Simultaneously, for the anti-obesity study, 24 neonate Wistar rats of 21-days old, divided into 2 groups of 12 rats (for obesity induction phase-1, for two weeks), and regrouped into 4 groups of 4 rats (14 days treatment phase-2), were used. Results: Result of LD50 on FLJ, RH, MFLJ, and EAFH showed no toxicity, no motility, and body weight of rats was not adversely affected evenup to 2000 mg/kg.The increased body weight of the HFD-obese rats was significantly (p&lt;0.05)reduced compared to control. There was significant (p&lt;0.05) decrease in activities of aspartate aminotransferase and alanine aminotransferase after MIX, MFLJ and EAFH administration, compared with control. Also, total protein and bilirubin concentrations was not significantly (p&lt;0.05) different compared to control. Administration of EAFH significantly (p&lt;0.05) reduced the concentrations of creatinine, urea, potassium, and chloride; while MIX and EAFH significantly (p&lt;0.05) increased their concentrations compared to control. Conclusion: It may be concluded that FLJ, RH, MFLJ, and EAFH are safe for consumption and also possess liver and renal protection. Peer Review History: Received: 27 October 2023; Revised: 19 November; Accepted: 28 December, Available online: 15 January 2024 Academic Editor: Dr. Asia Selman Abdullah, Pharmacy institute, University of Basrah, Iraq, asia_abdullah65@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Ahmad Najib, Universitas Muslim Indonesia, Makassar, Indonesia, ahmad.najib@umi.ac.id Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Dr. Gehan Fawzy Abdel Raoof Kandeel, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt, gehankandeel9@yahoo.com

Acute Oral Toxicity Study of Lepidagathis keralensis Madhus. &amp; N.P.Singh

Systematic documentation of local health tradition related knowledge is important for validating and preserving medicinal heritage of any place. Lepidagathis keralensis Madhus. &amp; NP Singh. is a species belonging to Acanthaceae family It is a perennial, prostrate, woody herb tenaciously attached to hard laterite soil. It is used by traditional practitioners of North Malabar for various ailments. Safety is of primary importance as far as any drug is concerned. No scientific data is available on the safety profile of this drug. Acute Oral toxicity study is the foremost step among toxicity studies. Hence this study was taken up. Aim &amp; objective: To assess the Acute Oral Toxicity of water extract of Lepidagathis keralensis Madhus. &amp; NP Singh. Materials and methods: Aqueous extract of the drug was orally administered in Wistar albino rats at different dose levels and various parameters for signs and symptoms of gross behavioural and physical changes starting from 30 minutes to 48 hours at various intervals were observed. Results and observations: The drug did not produce any signs of toxicity and mortality upto the dose of 2000 mg/kg in rats. Hence this drug which is extensively in use among traditional practitioners can be further studied and brought forward to main stream.

Acute and sub-acute toxicity study of anti-obesity herbal granules in Sprague Dawley rats.

Toxicological studies are essential for developing novel medications in pharmaceutical industries including ayurvedic preparation. Hence, the present study is aimed to evaluate acute and 28-days repeated dose oral toxicity of anti-obesity polyherbal granules (PHG) in Sprague Dawley rats by OECD guidelines No 425 and 407, respectively. In an acute oral toxicity study, a single dose of 2 g/kg PHG was administered to rats and mortality, body weight, and clinical observations were noted for fourteen days. However, in the subacute oral toxicity study, the PHG was administered orally at doses of 0.3, 0.5 and 1 g/kg daily for 28 days to rats. Food intake and body weight were recorded weekly. On the 29th day, rats were sacrificed and subjected to haematological, biochemical, urine, necropsy, and histopathological analysis. In an acute oral toxicity study, no treatment-related, mortality, behavioral changes, and toxicity were found throughout fourteen days. Likewise, in the sub-acute toxicity study, no mortality and toxic effects were found in haematology, biochemical, urine, necropsy and histopathological analysis in rats for 28 days of treatment with PHG. Based on these results, the LD50 of PHG was found to be greater than 2 g/kg and the no-observed-adverse-effect level (NOAEL) of PHG for rats was found to be 0.5 g/kg/day. Thus, anti-obesity polyherbal granules showed a good safety profile in animal studies and can be considered an important agent for the clinical management of obesity.

Toxicological Evaluation of a Polyherbal Formulation (18KHT01) and Validation of UPLC-DAD Method for Quality Control.

Background: 18KHT01 is a novel synergistic composition of Quercus acutissima, Camellia sinensis, Geranium thunbergii, and a small portion of Citrus limon. Our previous report demonstrated that the 18KHT01 exhibits potent antiobesity effects, with synergistic antioxidant, antiadipogenic, and antiobesity activities in diet-induced obese mice. This study explores the toxicity profile and quality control parameters of the 18KHT01 formulation. Methods: Broad-spectrum acute and subacute oral toxicity studies were performed using male and female ICR mice. In order to simultaneous analysis of the 18KHT01 formulation, an ultraperformance liquid chromatography coupled with a diode array detector (UPLC-DAD) method was developed and validated using six marker compounds. Results: Acute oral toxicity evaluation of 18KHT01, administered at single high doses of 2, 2.5, 3, and 5 g/kg, identified 2 g/kg as the no-observed adverse effect level (NOAEL). The LD50 (50% lethal dose) and LD100 (100% lethal dose) of 18KHT01 for male ICR mice were 3.99 and 7.77 g/kg, and those for the female mice were 2.94 and 4.70 g/kg, respectively. In addition, a 30-day repeated dose oral subacute toxicity evaluation indicated that 18KHT01 is safe below 500 mg/kg/day for long-term administration in ICR mice of either sex. UPLC-DAD method validation revealed that each calibration curve for the marker compounds showed good linearity, as well as the validation parameters such as precision, specificity, and accuracy met the acceptance criteria. Conclusion: The present study evidenced the toxicological profile of 18KHT01 polyherbal formulation in mice as well as developed a simple, rapid, and accurate chromatographic method for quality control.

Pharmacological screening of antidiabetic activity of ethanolic extracts of justicia tranquebarensis on streptozocin induced rats.

Non-communicable diseases like diabetes mellitus are becoming major health problem these days. There is an increasing demand by patients to use the natural products (plants) with anti-diabetic activity due to the severe side effects associated with the use of insulin and oral anti-diabetic drugs. One such plant is Justicia tranquebareinsis which has been traditionally used for the treatment of diabetes mellitus. The aim of this study was, therefore, to evaluate hypoglycemic activity of ethanol extract of Justicia tranquebareinsis in streptozotocin-induced diabetic rats, respectively and to carry out acute toxicity test. Two doses (200 mg/kg and 400 mg/kg) of the ethanol extract of Justicia tranquebareinsis were administered to normal glucose loaded and diabetic rat to study blood glucose lowering effect. Ethanol extract of Justicia tranquebareinsis (200mg/kg and 400mg/kg, p.o.) showed significant tolerance (P &lt; 0.05) to oral glucose load at 1 and 2 hrs after glucose load. The extract also produced significant (P &lt; 0.05) blood glucose reduction at 4 hours after its administration in normoglycemic mice. The extract at 400mg/kg dose level produced significant (P &lt; 0.05) reduction in blood glucose level at 2, 3 and 4 hours of treatment in streptozotocin (45 mg/kg) induced diabetic mice. Acute oral toxicity studies of ethanol extract of Justicia tranquebareinsis in rats showed no death or signs of toxicity at the dose of 2000 mg/kg indicating the safety nature of the extract. The results of the experiments showed that ethanol extract of Justicia tranquebareinsis has significant antihyperglycemic activity in streptozotocin induced diabetic rat and improvement in glucose tolerance and slight hypoglycemic activity in normal rat justifying the traditional claim for its use in diabetes.

Acute Effects of Brevetoxin-3 Administered via Oral Gavage to Mice.

Brevetoxins (BTXs) constitute a family of lipid-soluble toxic cyclic polyethers mainly produced by Karenia brevis, which is the main vector for a foodborne syndrome known as neurotoxic shellfish poisoning (NSP) in humans. To prevent health risks associated with the consumption of contaminated shellfish in France, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) recommended assessing the effects of BTXs via an acute oral toxicity study in rodents. Here, we investigated the effect of a single oral administration in both male and female mice with several doses of BTX-3 (100 to 1,500 µg kg-1 bw) during a 48 h observation period in order to provide toxicity data to be used as a starting point for establishing an acute oral reference dose (ARfD). We monitored biological parameters and observed symptomatology, revealing different effects of this toxin depending on the sex. Females were more sensitive than males to the impact of BTX-3 at the lowest doses on weight loss. For both males and females, BTX-3 induced a rapid, transient and dose-dependent decrease in body temperature, and a transient dose-dependent reduced muscle activity. Males were more sensitive to BTX-3 than females with more frequent observations of failures in the grip test, convulsive jaw movements, and tremors. BTX-3's impacts on symptomatology were rapid, appearing during the 2 h after administration, and were transient, disappearing 24 h after administration. The highest dose of BTX-3 administered in this study, 1,500 µg kg-1 bw, was more toxic to males, leading to the euthanasia of three out of five males only 4 h after administration. BTX-3 had no effect on water intake, and affected neither the plasma chemistry parameters nor the organs' weight. We identified potential points of departure that could be used to establish an ARfD (decrease in body weight, body temperature, and muscle activity).

Acute and subchronic oral toxicity study of Camelina sativa oil in Wistar rats

ObjectiveThe aim of these studies was to ascertain if Camelina sativa oil is harmful in both the acute and subchronic states. MethodsWistar rats of both sexes were used in an acute toxicity test, and the fatal dosage (LD50) of oral Camelina sativa oil was greater than 27.6 g/kg bw. Rats were gavaged with Camelina sativa oil at dosages of 0.00, 0.92, 1.84, and 3.68 g/kg bw per day for 90 days. In addition, satellite groups were established in the control and high-dose groups for a 28-day recovery period. The following factors were assessed: mortality, clinical anomalies, body weight, food intake, hematological, serum biochemistry, urine, gross necropsy, and histology. ResultsThere were no observable toxicity-related changes in any of the three dosage groups. There is no toxicological relevance to the change in the high-dose hematological indicator PLT at the conclusion of the recovery period because it was within the usual range for this strain in our laboratory. The test material did not result in any pathological alterations, according to a pathological examination. ConclusionSince the results of the current study, the no-observed-adverse-effect-level (NOAEL) for Camelina sativa oil in rats has been determined to be greater than 3.68 g/kg bw.

Evaluation of Anti-Inflammatory and Analgesic Property of Methanolic Extract of Momordica Dioica in Wistar Rat Model

Background: Since current medications frequently cause potentially serious side effects, countless individuals continued to have pain and inflammation despite the accessibility of treatments. Ancient practitioners have used a variety of herbal remedies with analgesic and anti-inflammatory properties extensively. Momordica Dioica is one of them, but no experimental research has been done in support of this traditional use. Objective: The purpose of the research was to assess the analgesic and anti-inflammatory properties of methanolic Momordica Dioica fruit extracts. Methods: Dryed by air According to OECD guideline the version eighteen, the fruit of Momordica Dioica is extracted with the solvent methanol as well as an acute oral toxicity study was done for the methanol-based extract of Momordica Dioica. The Active Constituent responsible for the Activity was confirmed by HPTLC method. The hot plate method was employed to assess the analgesic efficacy of centrally mediated analgesia.The ability to reduce inflammation was assessed using a carrageenan-induced paw oedema test. Results: Momordica dioica's methanolic extract inhibits the ceiling result during activity. The Methanolic Extract of Momordica dioica (MEMD) extract demonstrated a significant (p 0.0001) analgesic effect in the hot plate method at doses of 100mg/kg and in all combinations with standard. Maximum anti-inflammatory effects were seen in carrageenan-induced paw edema starting 2-4 hours after induction, and all tested doses of the extract significantly inhibited the carrageenan-induced inflammation (p 0.0001, p 0.001). The presence of a pentacyclic terpenoid i.e Ursolic acid present in the extract had potential analgesic and anti-inflammatory activity which supports the traditional claim.