Acute Oral Toxicity Study Research Articles

Toxicity profiling of Burgmansia aurea Lagerh. Leaves using acute and sub-acute toxicity studies in rats.

Toxicity studies in appropriate animal models are an integral and very important component of pre-clinical studies in drug development. Brugmansia aurea lagerh. is used for both medicinal and non-medical purposes, including treating skin infections, different types of physical discomfort, inflammation, cough, hallucinations, and evil protection. This study was designed to detect any hazardous effects of B. aurea on animals and find out its LD50. An acute toxicity study was performed to find out the LD50 value and sub-acute toxicity study was performed to find out the toxicity on repeated dose administration till 28 days. Both studies were performed according to the organization of economic cooperation and development (OECD) 425 and 407 respectively. For the acute oral toxicity study, animals were divided into two groups, group I normal control (NC) and group II received a 2000mg/kg dose of B.aurea leaves extract. In the sub-acute toxicity study, male and female animals were divided into eight groups, I-IV for males and V-VIII for females received control, 100, 200 & 400mg/kg B. aurea leaves extract respectively. Hematological and biochemical markers were estimated at the end of each study. Results revealed that no mortality and morbidity were observed in acute oral as well as sub-acute toxicity studies. Oxidative stress markers were increased significantly in all organs of the treatment groups in both studies. Animals significantly decreased their food and water intake in an acute oral toxicity study. A slight difference in renal function tests was observed in the acute oral toxicity study when compared with the normal control group. No significant change in histopathology was observed in both studies on selected organs. This study concluded that B. aurea can be safely used for pharmacological purposes.

Phytochemical Constituents and GC-MS Profiling of the Whole Plant Ethanol Extract of Thesium viride Hill and its Oral Toxicity in Balb/C Mouse Model

Thesium viride Hill, a member of the Santalaceae family, treats several ailments. However, few pharmacological investigations have been done to ascertain its folklore usage. The present study evaluated the presence of phytochemical constituents and Gas Chromatography-Mass Spectroscopy profiling of the whole plant extract of Thesium viride and its oral toxicity in the Balb/c mouse model. The whole plant-dried sample was collected from Zaria local government, Kaduna State, Nigeria, and 400 grams of the pulverised plant was extracted by the Soxhlet method using different solvents. Phytochemical screening and GC-MS analyses of the whole plant ethanol extract were done according to standard procedures. Acute oral toxicity studies of the extracts were carried out on BALB/c mice weighing 17-23g following recommendations from the OECD. The phytochemical analysis of Thesium viride whole plant extracts showed the presence of cardiac glycosides, carbohydrates, flavonoids, tannins, saponins, steroids, triterpenes, and alkaloids. In addition, the GC-MS analysis of the ethanol extract of Thesium viride revealed the presence of thirty-four bioactive compounds, the major ones being Bis (2-ethylhexyl) phthalate, cis-13-Octadecenoic acid, trans-13-Octadecenoic acid, n-Hexadecanoic acid, 9-Octadecenoic acid (Z), and Diethyl Phthalate with peak areas (concentrations) of 34.44%, 29.75%, 4.18%, 3.60%, 2.62%, and 2.01% respectively. The median lethal dose (LD50) for acute toxicity studies of different fractions of Thesium viride on Balb/c mice was greater than 5000 mg/kg. The study concludes that the whole plant extract of Thesium viride is rich in phytoconstituents with pharmacological prospects. The extract is practically non-toxic and safe when administered orally in mice.

Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy

BackgroundMorus alba Linn, referred to as white mulberry, is a potential traditional medicine for diabetes and neuroprotection. AimIsolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy. Material and methodsThe stem Bark of M. alba was peeled and subjected to extraction. A phytoconstituent was then isolated by column chromatography and characterized using Mass spectroscopy, FTIR, and NMR. The isolated phytoconstituent was used to formulate a nanoemulsion. Nanoemulsion was also characterized for viscosity, surface tension, refractive index, pH, and particle size. Selected nanoemulsion formulations were then tested for acute oral toxicity and diabetic neuropathy, including behavioral, hematological, histopathological, and biomarker examinations. ResultsThe spectral analysis affirmed that the isolated compound was found to be chrysin. A nanoemulsion formulation was made using the chrysin and was characterized and found to be stable during the stability testing and fulfilled all other testing parameters. Then acute oral toxicity study of the formulations was found to be safe. Formulations were found to possess significant results against diabetic neuropathy in rats. Biomarkers were analyzed for their mechanistic involvement in reducing neuropathy in rats, and it was found that the oxidative pathway was considerably restored, suggesting that chrysin causes these effects via this pathway. ConclusionsResults suggests that isolated phytoconstituent (chrysin) from the bark of Morus alba derived nanoemulsion has protective and beneficial effects by diminishing the oxidative damage against alloxan-induced diabetic neuropathy in rats.

Toxicological safety assessment of AP-Bio®, a standardized extract of Andrographis paniculata in Sprague Dawley rats.

Andrographis paniculata, commonly known as green chiretta, is a traditionally used plant in India, China, and Southeast Asian countries for its varied health benefits including immune health. The objective of the present study was to assess the safety of AP-Bio®, a standardized A. paniculata extract in Sprague Dawley rats by following the Organisation for Economic Cooperation and Development (OECD) test guidelines of acute and 90-day repeated dose sub-chronic toxicity studies. AP-Bio® did not show any treatment-related clinical signs of toxicity or mortality during the 14-day observation period in animals tested in the single-dose acute oral toxicity study up to a dose of 5000 mg/kg body weight. In the 90-day repeated dose sub-chronic oral toxicity study, no treatment-related adverse clinical signs were observed in any of the treated groups (300, 600, and 900 mg/kg). All treated animals showed usual weight gain and comparable feed intake. The ophthalmoscope examination did not reveal any abnormalities. Also, no toxicologically significant changes were observed in urinalysis, hematology, and blood chemistry parameters. Absolute organ weights and relative organ weights of vital organs did not differ significantly compared to control. Gross and histopathological findings did not show any remarkable and treatment-related changes. Results of the safety evaluation showed the median lethal dose (LD50 ) of AP-Bio® was found to be more than 5000 mg/kg rat body weight and the no observed adverse effect level (NOAEL) of AP-Bio® was found to be 900 mg/kg rat body weight.

Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200mg/kg, 2, 4, 8 and 10g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120mg/kg, I.P.) and two doses of AVFME (200 and 500mg/kg b.w., orally) were used as compared to glibenclamide (5mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. AVFME resulted in the highest phenolic content of 150.44±4.62mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38±0.97mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).

A 28-Day Repeated Dose Toxicity Evaluation of Creatinine Monohydrate and β-Hydroxy β-Methyl Butyrate Combination in Rodent Model

Substance abuse is a global concern, having a significant influence on society, healthcare, and the economy. Athletes are increasingly using substances to improve their performance or to cope with stress. Therefore, having a thorough awareness of the often misused substances, their effects, and potential toxicities is essential. One such chemical is the mixture of Creatinine Monohydrate (CM) and -Hydroxy Methyl Butyrate (HMB), which is widely used by athletes to increase strength and performance. According to studies, the combination can boost athletic performance, build muscle, and offer several health advantages. To determine the chemicals’ long-term impacts on human health, more research is required because their safety and toxicity are not well-established. Using TOPKAT(Computer-Aided Toxicity Prediction) and Discovery Studio Version 4.0, this study examined the toxicity and pharmacokinetic profiles of CM and HMB. The interaction of HMB and CM may significantly reduce cell viability compared to either drug alone. There were no negative effects seen in the animal models used for the acute oral toxicity study, but additional research is needed to confirm these results and determine the compounds’ long-term safety for human use. The study also performed cytotoxicity studies of individual substances and combinations on VERO and HEP-G2 cell lines and a 28-day repeated dose toxicity study in Wistar albino rats. The study results provide valuable information for healthcare professionals to understand the physiological complications of exposure to such drugs. Overall, the article emphasizes the importance of understanding the potential toxicity of chemical compounds, particularly those used as nutritional supplements.

Virtual Screening of Nrf2 Dietary-Derived Agonists and Safety by a New Deep-Learning Model and Verified In Vitro and In Vivo.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an essential regulatory target of antioxidants, but the lack of Nrf2 active site information has hindered discovery of new Nrf2 agonists from food-derived compounds by large-scale virtual screening. Two deep-learning models were separately trained to screen for Nrf2-agonists and safety. The trained models screened potentially active chemicals from approximately 70,000 dietary compounds within 5 min. Of the 169 potential Nrf2 agonists identified via deep-learning screening, 137 had not been reported before. Six compounds selected from the new Nrf2 agonists significantly increased (p < 0.05) the activity of Nrf2 on carbon tetrachloride (CCl4)-intoxicated HepG2 cells (nicotiflorin (99.44 ± 18.5%), artemetin (97.91 ± 8.22%), daidzin (87.73 ± 3.77%), linonin (74.27 ± 5.73%), sinensetin (72.74 ± 10.41%), and tectoridin (77.78 ± 4.80%)), and their safety were demonstrated by an MTT assay. The safety and Nrf2 agonistic activity of nicotiflorin, artemetin, and daidzin were also reconfirm by a single-dose acute oral toxicity study and CCl4-intoxicated rat assay.

Development of Novel Substituted 1,2,3,4-tetrahydro Cyclohex-1,2,3-trihydro Cyclopenta [B] Indole Derivatives as Potential Therapeutic Agents

Abstract: The current study aims to synthesize, characterize, and evaluate a specific class of heterocyclic compounds called fused polycyclic indoles, in combination with carbazoles, carbolines, and their partially saturated counterparts. These compounds have been known to have potent biological activity. The study's procedures involve synthesizing these compounds and evaluating them for central nervous system activity. Results showed that all the compounds had CNS-depressing effects in mice. Some compounds, such as YA1 and YA5, were found to have a stronger CNS-depressing activity than others. All compounds tested, YA1 to YA7, caused more than 50% change in locomotor activity when compared to a standard drug. YA3 and YA5 were found to have the highest activity at 86.2% and 83.9% respectively after 120 minutes of administration at a dose of 100 mg/kg. In addition, the acute oral toxicity studies showed that YA3 was non-toxic and YA5 was found to be toxic. The findings of the study provide evidence that these title compounds have good CNS activity.

Acute and Subacute Toxicity Studies of Ethanol, Chloroform extracts and Flower oil of Senecio edgeworthii hook plant

This study investigated the acute and subacute oral toxicity of SE- Oil, SE-Alcohol and SE-Chloro extracts of Senecio edgeworthii (SE) in a rodent for evaluating its safety profile. Senecio edgeworthii (SE) plant for the acute oral toxicity (300 to 5000mg/kg) and subacute oral toxicity SE- Oil (SE-Oil 50, 200, 500mg/kg) and SE-Chloro (SEC 100, 500, 1000mg/kg) and SE-Alcohol (SEA 100, 500, 1000mg/kg) studies were administered orally according to the guidelines 423 and 407 of OECD, respectively. In the acute oral toxicity study, doses are administered by 300mg/kg, 1000mg/kg, 2000mg/kg and 5000mg/kg (OECD guideline no. 423). SEA and SEC do not show toxicity up to 5000mg/kg; SE- Oil shows toxicity at a dose of 2500mg/kg. In the subacute toxicity study, the daily oral treatment with extracts of SEA and SEC 100, 500, 1000mg/kg, SE-Oil 50, 250, 500mg/kg of extracts for 28 days did not produce any death or hazard. Likewise, SEA and SEC 100, 500, 1000mg/kg, SE-Oil 50, 250mg/kg of Senecio edgeworthii hook no significant changes were recorded in food intake, body weight gain, the biochemical and haematological parameter of control and treated rats. SE-Oil 500mg/kg of significant changes were recorded in food intake and body weight gains are decreased compared to the control group and SE-Oil 500mg/kg there was a significant (P &lt; 0.05) decrease in RBC counts in the treated animals compared to that of the control group counts in the treated animals and induction (ALT, AST, and alkaline phosphatase and Total protein). SE- Oil 500mg/kg of extract treaded group saw mild liver pathological findings characterized by abnormal hepatic configuration was observed with treated animals. The present result from the acute and subacute toxicity study Senecio edgeworthii hook alcohol and chloroform extract is considered relatively safe on acute and subacute oral exposure. Senecio edgeworthii hook flower hexane extract shows acute toxicity at dose 2500mg/kg and in subacute toxicity study, higher dose 500mg/kg.

Prenatal Developmental Oral Toxicity Evaluation of Defatted Fenugreek Seed Flakes (FenuflakesTM) in Laboratory Rats

Fenugreek seed-based ingredients showed potential health benefits towards female-specific conditions. The present work is aimed to assess the prenatal oral toxicity of fibers and protein rich defatted fenugreek seed flakes (Fenuflakes™). The acute oral toxicity and dose range-finding studies in non-pregnant and pregnant rats were conducted before the main study. The selected doses of Fenuflakes (500, 1000, and 2000 mg/kg) were orally gavaged to rats daily from day 0 to day 19 (one day before the expected day of parturition) post-conception with the concurrent vehicle control (VC) group. On the 20th day of gestation, the maternal and embryo-fetal toxicity parameters were recorded after the cesarean sections of dams. Results: Fenuflakes in tested doses exposure did not show significant toxicological changes in maternal (body weights, food intake, anogenital distance, or clinical observations) and embryo-fetal evaluations (number of corpora lutea, resorptions, and implantations, or fetus weights, sex ratio or incidence of anomalies) compared with VC. Conclusion: Oral prenatal exposure to Fenuflakes was found safe with no significant maternal and embryo-fetal toxicities. The "No Observed Adverse Effect Level” (NOAEL) of Fenuflakes (&gt; 2000 mg/kg/day) can be used for risk assessment before human consumption in pregnant female population.

Fabrication of nanoparticulate system for oral delivery of Naringenin against paraquat-induced Parkinson's disorder in Wistar rats

BackgroundParkinson's disorder (PD) is a neurodegenerative condition associated with slow movement, tremors, imbalance, bradykinesia, and rigidity with advanced complications like sleep disorder, pains, sensory disability, and cognitive impairment. As per World Health Organization, PD is the leading neurological disorder worldwide. Although Parkinson's disorder cannot be cured, medications might significantly improve the symptoms. Current treatment for Parkinson's disorder includes cell implantation, Gene therapy, Surgical approaches, and Rehabilitation. But there are several adverse effects associated with these treatment methods which can be addressed using nanoparticles that possesses the ability to cross the blood-brain barrier, increased stability against enzymatic degradation, lowers liver toxicity, etc. Several Phyto-constituent have proven their role in the management of Parkinson's disorder. One such natural flavonoid is Naringenin, which is been reported to have diverse neuronal effects. Materials and methodsIn the first part, the Naringenin-loaded PLGA nanoparticles were fabricated by using a single emulsion solvent emulsion method. Optimization was performed by using a 32-factorial design to investigate the impact of independent variables viz. PLGA concentration and number of HPH cycles. The optimized batch was spray-dried and evaluated for DSC, XRD, and SEM to confirm desired characteristics. LD50 was determine by performing Acute Oral Toxicity (AOT) study as per OECD-420 guidelines. Parkinson was induced by injecting rats with paraquat (i.p.) twice a week for 6 weeks. Simultaneously, nano-suspension and standard drug were also administered orally to respective group 60min prior to paraquat every day for 6 weeks. After 42/45 days parameters like Gross examination of the brain, Relative brain weight determination, behavioral parameters, biochemical evaluation (MDA, SOD, CAT, GSH, α-synuclein protein levels), and immunohistochemistry (BDNF level) investigation were performed. Brain histopathological study was performed to support the findings. ResultsAn optimized batch of Naringenin-loaded PLGA nanoparticles showed particle size, PDI, and %EE as 162.1 ​nm, 0.288, and 91% respectively. Spray-dried nanoparticles were found to be spherical during SEM analysis which may facilitate the easy movement of nanoparticles through different barriers. The DSC and XRD study confirmed the molecular dispersion of the drug. In vivo studies showed quite promising results through behavioural, histopathological, biochemical, and immunohistochemistry evaluations. ConclusionsIn conclusion, Naringenin-loaded PLGA nanoparticles showed a protective effect on the levels of MDA, SOD, CAT, GSH, α- Synuclein protein, and BDNF and prevented the neurodegeneration in brain tissue in Paraquat-induced Parkinson's disorder. Based on the outcomes of present study, the use of Naringenin-loaded PLGA nanoparticle dispersion is the promising alternative available to Parkinson's disorder treatment.

Phytochemical investigation and exploration of the central nervous system depressant activity of ethanolic extract of the flowers of Jasminum grandiflorum L. as folklore medicine in Swiss albino mice

Background: In Indian traditional medicine, the flowers of Jasminum grandiflorum L. (Oleaceae) are claimed to possess powerful central nervous system (CNS) depressant activity. Despite these traditional claims, no in-depth scientific study has been performed on the CNS depressant activity of the flowers of J. grandiflorum. Therefore, the present study was aimed at evaluating the CNS depressant activity of an ethanolic extract of the flowers of J. grandiflorum in Swiss albino mice.&#x0D; Methods: Acute oral toxicity tests were done at doses of 550, 1750, and 5000 mg/kg. The extract was also subjected to phytochemical tests and TLC tests. The CNS depressant activity of the EEJG was evaluated by various models, such as the forced swimming test, tail suspension test, thiopental sodium-induced sleeping time test, locomotor activity test, and muscle co-ordination test, at two different doses (500 and 1000 mg/kg) in Swiss albino mice. Diazepam (1 mg/kg) was used as a standard drug.&#x0D; Results: In acute oral toxicity studies, the extract was found to be safe up to a dose level of 5000 mg/kg body weight. EEJG at both doses (500 and 1000 mg/kg) showed significantly (p&lt;0.05, p&lt;0.01) increase in immobility time in the forced swimming test and tail suspension test. In the thiopental-induced sleeping time test, EEJG at 1000 mg/kg showed a significant (p&lt;0.05) effect on the onset of action time and also significantly (p&lt;0.01) increase the duration of sleeping time. EEJG at 1000 mg/kg showed a significant (p&lt;0.01) decrease in locomotor activity, and the EEJG at both doses (500 and 1000 mg/kg) showed a significantly (p&lt;0.05, p&lt;0.01) decreased in muscle co-ordination activity when compared to control group.&#x0D; Conclusions: The present study confirms the significant CNS depressant activity of the ethanolic extract of the flowers of J. grandiflorum, which may be due to flavonoids and steroids present in the extract as phytoconstituents confirmed by TLC. This study supports the plant's traditional use as a CNS depressant.

Assessment of metabolic stability, pharmacokinetics by LC-MS/MS and establishment of safe dose of IMID-2, a novel anticancer molecule under drug discovery.

Pyruvate kinase (PK) M2 activators ramp up glycolysis in cancer cells leading to a reversal of the Warburg effect in cancer cells. A promising PKM2 activator molecule IMID-2 developed by National Institute of Pharmaceutical Education & Research, Ahmedabad (NIPER-A) showed promising anticancer activity against MCF-7 and COLO-205 cell lines which represent breast and colon cancer. Its physicochemical properties like solubility, ionization constant, partition coefficient, and distribution constant have already been established. Its metabolic pathway is also well established through in vitro and in vivo metabolite profiling and reported previously. In this study, we have evaluated the metabolic stability of IMID-2 using (LC-MS/MS and investigated the safety aspect of the molecule through an acute oral toxicity study. In vivo studies in rats confirmed that the molecule is safe even at the dose level of 175 mg/kg. Furthermore, the pharmacokinetic study of IMID-2 was also carried out by LC-MS/MS to understand its ADME profile. The molecule was found to have promising bioavailability through the oral route. This research work is thus another step toward drug-likeness testing of this promising anti-cancer molecule. The molecule can be considered to be a potential anti-cancer lead based on the earlier report substantiated by current findings.

Toxicity Status of Nano Powder of Stem Bark of &lt;i&gt;Bauhinia Variegata&lt;/i&gt; Linn. on Experimental Animals

The assumption that medicinal plants are less toxic or cause fewer adverse effects due to their natural composition is debatable. Hence, this study was conducted to evaluate the safety and toxicity of Nano Kanchanara stem bark powder (NKSP) on liver function. The oral acute toxicity of NKSP was conducted in accordance with OECD Guidelines 423 and was carried out with six (6) female Wistar albino rats, divided into two groups of three rats each. Test rats were orally administered a single dose of 2000 mg/kg of NKSP and were observed for changes in behavior and mortality for the next 14 days, while the Control Group was given feed and water ad libitum. The data obtained from the oral acute toxicity study indicated that there were non-significant (P&lt;1.000) decreases in body weight of rats in the treatment groups of NKSP at 2000 mg/kg. There were no elevations in specific liver function enzymes, whereas there were increases in serum SGOT, SGPT, and albumin levels. Plasma total proteins and globulin, total bilirubin and serum creatinine were within the normal range. Albeit, hydropic changes and steatosis in liver lesions at NKSP 2000 mg/kg. The study suggests that oral administration of NKSP is safer at dose levels less than 2000 mg/kg/day.

&lt;i&gt;Camphora&lt;/i&gt; Augments Humoral Mediated Immunity and Decreases Delayed type Hypersensitivity in BALB/c Mice

Background: Immunomodulation encompasses all therapeutic interventions aimed at modifying the immune response. The immune response augments are desirable to prevent infection in immunodeficiency states and fight established diseases. In this context, the present study investigated the effect of the homeopathic medicine, Camphora, in 6CH, 30CH, and 200CH potencies on immunomodulation in experimental animals. The acute oral toxicity study was also carried out in 6CH, 30CH, and 200CH potencies to determine the safe dose volume for the immunomodulatory study. Methodology: Acute oral toxicity studies of Camphora in 6CH, 30CH, and 200CH potencies were carried out as per OECD guideline 423 with slight modifications in Wistar albino rats. Humoral immunity, i.e., primary and secondary humoral responses, was assessed by measuring the hemagglutination titre of sheep red blood cells. Delayed-Type Hypersensitivity (DTH) was evaluated by measuring footpad thickness in BALB/c mice. Results: Camphora in 6CH, 30CH and 200CH potencies at a dose volume of 2000 µl/kg did not cause any mortality in the rats when administered as a single dose. Camphora in 6CH, 30CH and 200CH potencies showed augmented primary and secondary humoral responses against the SRBC antigen in BALB/c mice. However, the values were statistically non-significant except in the case of 6 CH potency (p&lt;0.01), which showed statistically significant primary anti-SRBC antibodies. In the DTH assay, Camphora in 6CH, 30CH and 200CH potencies significantly decreased the paw volume ratio after 24 hrs of SRBC injection in the paw, thus insinuating its role in reducing cell-mediated immunity. Camphora in 6CH, 30CH and 200CH potencies also showed enhanced antibody titres and decreased paw volume compared to vehicle control, i.e. dispensing alcohol, suggesting that the effect was imminent because of Camphora. Conclusion: The study results indicate that Camphora in 6CH, 30CH, and 200 CH potencies is safe up to a dose volume of 2000 µl/kg when administered as a single dose, augments the primary and secondary humoral immunity, and decreases DTH in experimental animals. The current study’s findings suggest that Camphora might be useful as an immunomodulator in treating immune system disorders and infectious diseases and require further investigation to investigate its mechanism of action.

Acute and Repeated Dose 28-Day Oral Toxicity Studies of Phlorotannin Rich Fraction of &lt;i&gt;Sargassum tenerrimum&lt;/i&gt;, A Marine Brown Algae

Sargassum tenerrimum is a marine brown algae rich in phlorotannins, a class of marine polyphenols with significant biological activities. The present study aimed to prepare a phlorotannin-rich fraction from S. tenerrimum (PST) and evaluate its acute and subacute oral toxicity in Wistar albino rats according to the procedures and methods of the OECD test guidelines for acute and repeated dose 28-day oral toxicity studies. S. tenerrimum powder was extracted with ethanol and further fractionated with ethylacetate, 1-butanol, and water. The ethyl acetate fraction was found to have the highest total phlorotannin concentration and was evaluated for its safety. In the acute oral toxicity study, a single dose of PST at 2000 mg/kg body weight did not result in any treatment-related clinical symptoms of toxicity or mortality. Therefore, the median lethal dose (LD50) of PST was identified as greater than 2000 mg/kg. The subacute oral toxicity investigation at 200, 400, and 800 mg/kg doses administered for 28 days with a 14-day recovery period revealed no treatment-related adverse clinical symptoms or mortality/morbidity. The treated animals exhibited normal weight gain, feed intake and did not result in clinically significant toxicity as measured by clinical blood chemistry and hematological markers. Gross and histological examinations of selected tissues did not reveal any notable adverse alterations associated with the intervention. Under the study's findings, the LD50 for PST was determined to be &gt;2000 mg/kg b.wt. and No Observed Adverse Effect Level (NOAEL) to be 800 mg/kg rat b.wt.

Evaluation of acute oral toxicity of Ipomoea turpethum extract loaded polymeric nanoparticles in Wistar rats.

Introduction: The amalgamation of novel drug delivery techniques and potential drugs is considered the most promising tool for the treatment of diseases. In our study, we have employed N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid (NIPAAM-VP-AA) copolymeric nanoparticles for delivering Ipomoea turpethum root extract. I. turpethum is a perennial herb (Convolvulaceae family) and has been used as medicine for ages. The present study was conducted to evaluate the safety of I. turpethum root extract-loaded NIPAAM-VP-AA polymeric nanoparticles (NVA-IT) in Wistar rats. Methods: An acute oral toxicity study was conducted in accordance with OECD guidelines 423 for the testing of chemicals. Different doses of NVA-IT i.e., 5mg/kg, 50mg/kg, 300mg/kg, and 2000mg/kg were administered to female Wistar rats in a stepwise manner using oral gavage. The toxicity signs were thoroughly observed for the next 14days. At the end of the study, the blood and vital organs were harvested for hematological, biochemical, and histopathological studies. Result: No mortality or pathological anomalies were observed even at the highest dose which exemplifies that the lethal dose would be more than 2000mg/kg body weight (GSH category 5). Behavioral changes, biochemical parameters, and histopathology of vital organs were normal after NVA-IT administration. Conclusion: This study demonstrated that NVA-IT nanoparticles are non-toxic and can be considered for therapeutic use in different diseases, such as inflammation, CNS diseases, Cancer, etc.

Acute and sub-chronic oral toxicity studies of “Tri 02” powder in experimental animals

This study aims to assess the acute and sub-chronic oral toxicity of “Tri 02” powder in experimental animals. According to World Health Organization Guidance, acute toxicity study was conducted using Swiss mice. LD50 was determined by Litchfield-Wilcoxon method, and sub-chronic toxicity of “Tri 02” at two doses (2.4 g/kg b.w/day and 7.2 g/kg b.w/day) was assessed in Wistar rats for four uninterrupted weeks. Abnormal behavior, toxic symptoms, and death were observed for 7 consecutive days to assess the effects of acute toxicity. The general behavior of the rats was observed daily, and their body weight was recorded weekly. Hematological analysis and biochemical analysis were conducted before treatment, and at 2 and 4 weeks of treatment. Macroscopic examination and histopathological examination of several organs were conducted at the end of the treatment period. The results suggested that “Tri 02” at the highest dose used for mice (187.5 g/kg b.w) did not show acute toxicity and the LD50 was determined. In terms of the sub-chonic toxicity test, after oral administration of “Tri 02” powder, hematological parameters, hepato-renal functions and microscopic images of liver and kidney at both doses were similar to the control group. In conclusion, “Tri 02” powder did not produce the acute and subchronic oral toxicity in experimental animals.

Anti-nociceptive potential of an isatin-derived dual fatty acid amide hydrolase-monoacylglycerol lipase inhibitor.

Recently, we have reported an isatin-derived carbohydrazone, 5-chloro-N'-(6-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (SIH 3) as dual nanomolar FAAH (fatty acid amide hydrolase)-MAGL (monoacylglycerol lipase) inhibitor with good CNS penetration and neuroprotective activity profile. In this study, we further investigated the pharmacological profile of compound SIH 3 in the neuropathic pain model along with acute toxicity and ex vivo studies. Chronic constrictive injury (CCI) was used to induce neuropathic pain in male Sprague-Dawley rats and the anti-nociceptive activity of the compound SIH 3 was investigated at 25, 50, and 100mg/kg ip. Subsequently, locomotor activity was measured by rotarod and actophotometer experiments. The acute oral toxicity of the compound was assessed as per the OECD guidelines 423. Compound SIH 3 showed significant anti-nociceptive activity in the CCI-induced neuropathic pain model without altering the locomotor activity. Furthermore, compound SIH 3 showed an excellent safety profile (up to 2000mg/kg, po) in the acute oral toxicity study and was also non-hepatotoxic. Further, ex vivo studies revealed that the compound SIH 3 produces a significant antioxidant effect in oxidative stress induced by CCI. Our findings suggest that the investigated compound SIH 3 has the potential to be developed as an anti-nociceptive agent.

Phytochemical analysis and in vitro and in vivo antioxidant properties of Plagiorhegma dubia Maxim as a medicinal crop for diabetes treatment

In traditional medicine, Plagiorhegma dubia Maxim (PD) is used to treat diabetes, irritability, insomnia, high fever, and coma. In this study, to identify the components in PD, we first performed three preliminary phytochemical tests, which were all positive for the presence of alkaloids. Next, we evaluated the total alkaloid content and performed 13 different in vitro antioxidant experiments for three solvent extracts of PD. According to the results, the methanol extract was selected for further research. Ultra-performance liquid chromatography with electrospray ionization Orbitrap mass spectrometry was used to identify 41 compounds in the methanol extract. Thirty-eight of these compounds were alkaloids, and the main components were magnoflorine, berberrubine, and betaine. Addition of the methanol extract to cooking oil increased the stability against oxidation and greatly reduced the peroxide value. Cell viability and oral acute toxicity studies in mice indicated that the methanol extract was relatively non-toxic. Histopathological examination and biochemical analysis showed that the methanol extract was protective against liver damage in rats induced by d-galactosamine. The methanol extract also showed a good antidiabetic effect for streptozotocin-induced diabetes in rats, where it lowered blood sugar levels and protected vital organs against damage. Lipid profile parameters and oxidative stress parameters also improved. The therapeutic effects towards diabetes and liver damage were attributed to the ability of the three main components in the methanol extract to resist oxidative stress. Our results show that the alkaloid-rich methanol extract of PD is potential candidate for treatment of diseases associated with oxidative imbalances. This understanding of the hepatoprotective effect and antidiabetic activity of PD provides new insight for its use as a substitute for Coptis chinensis and establishes a foundation for development of PD as an economic crop.