Subacute Toxicity Research Articles

Evaluation of the Acute and Subacute Toxicity of Aqueous Extract of Coriandrum sativum L. Seeds in Wistar Rats.

In traditional herbal medicine, the Coriandrum sativum (CS) seeds are widely used to prevent and/or treat several diseases. Despite this, research into studying their toxicity is very limited. This study aims at studying the acute and subacute toxicity of aqueous extract of coriander seeds (AECS) in Wistar rats. For acute toxicity, five dose levels (500, 1000, 2000, 3000, and 5000 mgkg-1bw) were tested per single oral administration. Subacute toxicity for 28 days was achieved by daily oral administration of AECS at doses of 1000, 2000, and 3000 mgkg-1bw. No deaths or signs were recorded or observed in rats in the five groups and the control group was after 14 days of acute toxicity study. The results of subacute toxicity revealed that the administration of AECS caused a significant difference in the body weight of rats at doses of 2000 and 3000mgkg-1bw, and in the development of movement disturbances, hypoactivity, drowsiness, weakness, and diarrhea, while histopathological examination showed vascular congestion and inflammation of the kidneys as well as hepatic necrosis. The haematological profile showed a significant increase in the number of red and white blood cells, haemoglobin, haematocrit, and a nonsignificant decrease is noticed in neutrophils at a dose of 3000 mgkg-1bw. AECS should be used with caution as it has caused some signs of toxicity and may affect the liver and kidneys if doses are repeated. However, further studies are needed to verify and clarify the toxic aspect of Coriandrum sativum L. seeds.

Acute and Sub-Acute Toxicity Evaluation of the Crude Methanolic Extract of Justicia schimperiana Leaf in Wistar Albino Rats.

This study evaluates the acute and sub-acute toxicity of 80% methanolic extracts of the leaves of Justicia schimperiana in Wistar albino rat models. Dried powdered leaves of Justicia schimperiana were macerated in 80% methanol. The experiment was conducted in accordance with the Organization for Economic Co-operation and Development guideline 423 for acute and 407 for sub-acute toxicity testing. A single dose of 5000 mg/kg extract was orally administered to three female rats for the acute toxicity study. The plant extract was administered orally for 28 days in daily dosages of 250, 500, and 1000 mg/kg for the sub-acute study. Animals in a control group were given distilled water. A total of 40 rats (5 rats/group/sex) were used for the sub-acute toxicity testing. Daily food intake and weekly body weight measurements were done. The rats were sacrificed at the end of the 28-day treatment period for hematological, biochemical, and histopathological tests. One-way analysis of variance and Kruskal-Wallis tests were employed for the analysis. The single-dose oral administration of the plant resulted in no deaths or serious morbidity. The median lethal dose was >5000 mg/kg. The 28-day oral treatment of the plant extract had no significant effect on general behavior, food intake, organ weight, biochemical parameters, or the majority of the hematological markers, with the exception of the decrease in hemoglobin and hematocrit in the 1000 mg/kg extract-treated groups compared to the controls. Both sexes experienced significant weight increases at all dosage levels. With the exception of minor alterations in a few of the organs, no significant histological change was identified. It is concluded that the single-dose and repeated-dose 28-day oral administration of the methanolic leaf extract of Justicia schimperiana is relatively safe.

Sub-Acute Toxicity Study of Hydro-Alcoholic Extracts of <i>Sansevieria cylindrica</i> and <i>Plumeria obtusa</i> in Wistar Albino Rats

Sansevieria cylindrica Bojer ex. Hook (Asparagaceae) and Plumeria obtusa L. (Apocynaceae) are useful traditional medicines. The present study assessed the toxicity of a combination of hydro-alcoholic extract of aerial parts of both these plants through repeat administration in Wistar albino rats. This study is an extension of an acute toxicity study, wherein female rats were orally administered with a single dose of 2000mg/kg of both plant extracts. Sub-acute toxicity of both plants (200 and 400 mg/kg p.o.) was studied by daily dosing of Wistar rats of both sexes for 28 days. Toxicity, mortality, body weight changes, food and water intake, and neurological assessments were recorded. Hematological, biochemical, and urine analysis was done before and after dosing on day 29. Absolute and relative organ weight and histological evaluation were performed on day 29. The acute toxicity study revealed no lethal effects indicating that LD50 is greater than 2000mg/ kg. The sub-acute study observed a significant increase (p < 0.05) in body weight, feed, and water intake. The body weight gain in rats from the treatment group was non-significant (p > 0.05) compared to the control group. A significant (p < 0.05) increase in lymphocytes, granulocytes, RBC, platelet, creatinine, albumin, triglycerides, and alkaline phosphatase were also observed. The evaluation of different neurobehavior parameters showed a significant increase (p < 0.05). Histopathological analysis showed mild liver distortion in male rats in both treatment groups. Most of the significant observations were considered incidental findings indicative of low toxicity of plant extract during long-term use.

Acute and sub-acute oral toxicity assessment of the methanol root extract of Olax subscorpioidea Oliv. (Olacaceae) in mice and rats

Olax subscorpioidea Oliv. is an important medicinal plant included in African traditional anticancer medicines. Little information about its safety and toxicity appears in the literature. This study thus aimed at evaluating the safety of its methanol root extract orally administered in laboratory animals. Fourier Transform Infrared (FTIR) spectrophotometric analysis of O. subscorpioidea extract was conducted. For acute toxicity, methods within the Organization for Economic Co-operation and Development (OECD) guidelines were used, with slight modifications. A single female mouse was orally administered a dose of 2,000 mg/kg body weight of O. subscorpioidea methanol root extract and was monitored for at least 24 h for any signs of toxicity or death. An additional four mice (n = 4, 2/sex) were similarly treated. Another female mouse was orally administered 5,000 mg/kg body weight and observed for at least 24 h. Additional four mice were similarly treated. For sub-acute toxicity, the extract was administered daily to Wistar rats for 21 days at 250 mg/kg, 500 mg/kg, and 1,000 mg/kg. General behaviours changes, haematological, biochemical, and histological examinations on rats’ organs were performed. The FTIR spectrum showed no peaks in the 2220–2260 cm−1 region, suggesting that no cyanide groups were present in the extract. A single oral dose at both 2000 mg/kg and 5000 mg/kg did not induce any signs of toxicity or mortality, indicating an oral median lethal dose (LD50) >5000 mg/kg. When compared to the controls, dose-dependent changes were observed in the red blood cells, haemoglobin and haematocrit levels at 500 mg/kg and 1000 mg/kg (p<0.05). Histopathological examinations showed severe vascular congestion in the liver, and interstitial congestion and haemorrhage with moderate glomerular damage in the kidney. This study showed O. subscorpioidea root's methanol extract as non-toxic in acute administration, but with potential for toxicity in sub-acute oral administration.

Pharmacognostic characterization, wound healing and toxicity assessment of the stem bark of Xylia evansii Hutch (Leguminosae)

Xylia evansii is widely used in traditional medicine to stop bleeding gums and treat wounds. This study was undertaken to assess the wound healing activity and toxicity profile of the stem bark methanol extract of X. evansii (XES). Wound healing activity was determined by the dermal excision model in rats. The free radical scavenging capacity, antioxidant activity, total phenolic and flavonoid contents were evaluated by the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, total antioxidant capacity (TAC), aluminum chloride colorimetric and Folin Ciocalteu methods respectively. Acute and sub-acute oral toxicity assessment was performed following the Organization for Economic Co-operation and Development guidelines. Significant (p < 0.05) dose-dependent wound healing effect, similar to that of 1 % silver sulphadiazine was elicit by the 10, 15 and 20 %w/w XES ointments. The highest effect was demonstrated by XES 20 %w/w which resulted in 98.3 % wound surface closure by day 9 of treatment (p < 0.0001). The total phenolic and flavonoid contents were determined to be 381.2 ± 12.57 mg/g gallic acid equivalent (GAE) and 460 ± 29.07 mg/g quercetin equivalent respectively. XES exhibited remarkable free radical scavenging effect (IC50 = 68.13 ± 1.87 μg/mL) and had a total antioxidant capacity of 279.2 ± 32.08 mg/g GAE. The LD50 of XES was estimated to be > 5000 mg/kg. In sub-acute toxicity, 28 days treatment with XES (250, 500, 1000 mg/kg body weight) did not result in any significant (p > 0.05) change in the body weight or weight of the heart, lung, spleen, liver and kidneys. The haematological and biochemical profiles of XES-treated rats were not significantly (p > 0.05) affected after 4-weeks treatment with XES, except for platelet count which increased significantly (p < 0.0001) in a non-dose-dependent manner. Histopathological examination did not reveal any toxic effect to liver cells, however at 1000 mg/kg XES, slight abnormalities were identified in the glomeruli. Microscopy of the powdered stem bark displayed calcium oxalate crystals, pitted vessels and lignified fibres. Tannins, flavonoids, coumarins, saponins, triterpenes and alkaloids were identified in the bark. This is the first report on the wound healing potential and safety profile of X. evansii, giving scientific credence to its use in traditional medicine.

Biomarkers of oral subacute toxicity of deltamethrin in exposed male Albino rats.

Deltamethrin is one of the most effective pyrethroid compounds, widely employed in veterinary medicine, public health, and farming. Deltamethrin-triggered oxidative stress largely causes serious harm to an organism. Acute toxicity of this compound was extensively investigated, while less information is available on its oral sub-acute effects. This study assessed, in the male Albino rats, the effects of oral gavage of either 0.874mg/kg (0.01 LD50) or 8.740mg/kg (0.10 LD50) of deltamethrin for successive 14days to investigate its effects on biomarkers and to detect the tissue injury in rats following subacute deltamethrin treatment. It was found that levels of glutathione peroxidase, superoxide dismutase, and catalase in the brain, kidney, and liver, alkaline phosphatase (ALP), and uric acid in serum, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC)s, eosinophils, and basophils were significantly reduced compared with untreated rats. However, when rats were treated with deltamethrin for successive 14days, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities in serum and the levels of thiobarbituric acid reactive substances (TBARs) in brain, kidney, and liver, red blood cell distribution width (RDW-CV), total protein, monocytes, and basophils and the ratios of neutrophils to lymphocytes, an aggregated marker of systemic inflammation and systemic immune inflammation indexes, significantly increased compared with the control group. Histologic lesions were observed in the liver, kidney, brain, testis, and epidemies in rats exposed to subacute deltamethrin for 14days, and most tissues of rats treated with 0.10 LD50 of deltamethrin were more affected than those treated with 0.01 LD50. These findings strongly suggest that subacute exposure to deltamethrin caused significant systemic toxicity through oxidative stress resulting in biochemical and histological changes in the studied tissues. These findings highlight the potential harmful effects of deltamethrin and emphasize the importance of understanding the subacute effects of this compound, particularly in the context of veterinary medicine, public health, and farming.

Sub-acute toxicity evaluation of aqueous leaf extract from Passiflora edulis Sims f. edulis (Gulupa) in Wistar rats

The genus Passiflora (Passifloraceae) comprises about 500 species. The Passiflora edulis stands out because of its economic and medicinal importance. It is widely planted in tropical and subtropical regions worldwide, especially in South America, the Caribbean, South Africa, and Asia. The aqueous extract of Passiflora edulis Sims f. edulis (Gulupa) leaves is used in traditional medicine for its soothing and tranquilizing effects on the central nervous system. Therefore, evaluating its safety for human use is a fundamental requirement to continue the development of new therapies within the framework of regulatory, preclinical, and clinical guidelines. Here, the sub-acute toxicity study was conducted following the Organization for Economic Cooperation and Development (OECD) guideline 407 for 28 days in Wistar albino rats. The study showed that 1000 mg/kg/day of the aqueous extract in 10 adult Wistar rats (five males and five females) was well tolerated. The hematological results are at normal levels. However, monocytopenia and eosinopenia were observed with a significant difference (P < 0,05) for both male and female rats treated with the aqueous extract of Passiflora edulis. The results show that liver and kidney function profiles were conserved. However, an increase in ALT is observed with significant differences between male and female rats treated with the extract compared to the controls. Study findings were limited to non-adverse histopathological results of a slightly increased incidence of focal periportal lymphocytic infiltrate in the liver and focal corticomedullary nephrocalcinosis in the kidney compared to control. Therefore, the aqueous extract of Passiflora edulis has a good safety profile in oral administration, was well tolerated, and did not cause any lethality or adverse effects in the sub-acute toxicity study in male and female rats. The NOAEL (no observed adverse effect level) for the 28-day subacute toxicity study was considered to be 1000 mg/kg.

Acute and Subacute Toxicity of Ruta Montana Extract to Female Rats: Effect on Liver, Kidneys and Ovaries

Ruta montana L. is an annual aromatic plant of the family rutaceae. Quantitative analysis of the methanolic crude extract of Ruta montana L. yielded 8.43%, whereas the qualitative analysis revealed the presence of alkaloid or coumarin. The Litchfield and Wilcoxon method calculated the LD50 of the crude methanolic extract of Ruta montana L. in Wistar albino female rats at 393.18 mg/kg. This allows the plant to be classified as moderately toxic. The subacute toxicity study of the methanolic crude extract of Ruta montana L. in female Wistar albino rats treated with 100 mg/kg (≈ 1/4 LD50) and intraperitoneally showed a significant increase in body weight of the rats treated at the 4th week. Animals treated and sacrificed after 30 days showed a disturbance of the relative mass of the organs. Biochemical parameters of hepatic function assessment showed a significant increase in PAL with elevation of AST and ALT, whereas those of renal function revealed a significant decrease in creatinine with an increase in urea. Hematologic parameters recorded a decrease in RBC, HGB and HCT. The histological sections of the treated rats reveal the existence of blood congestion in the central veins and liver tissues, foci of necrosis and steatosis in the liver, blood congestion and some glomerular atrophy in the kidneys, as well as blood congestions and developed follicles without oocytes in the ovaries.

Evaluation of Subacute Toxicity of Flavonoid from Phaleria Macrocarpa Fruit Extract in Mice

Background: Traditional medicine and supplements including Phaleria macrocarpa or Mahkota Dewa are extensively utilised. Rape fruit of phaleria macrocarpa contains flavonoid as a secondary metabolite that has a beneficial effect on endometriosis treatment and other illnesses. The purpose of this study was to look into the subacute toxicity of flavonoid from phaleria macrocarpa fruit extract on the brain and heart of BALB/c female mice. Method: The BALB/c female mice aged 6-8 weeks with a body weight of 20-30gr were divided into four groups and treated for 28 days. The control group received simply water, whereas the treatment group received flavonoid at doses of 500mg/kg/day, 1000mg/kg/day, and 2000mg/kg/day. At the end of the experiment, the mice were sacrificed and important organs were extracted and assessed. The organ weight was assessed using macroscopy, and the brain and heart were assessed using microscopy (histopathological abnormalities). Result: The BALB/c female mice treated with oral administration flavonoid from phaleria macrocarpa fruit extract showed no clinical abnormalities and no change in organ weight compared to the control groups (p&gt;0,5) in subacute toxicity experiments. There were no abnormalities in the organs of the treated mice at a dose of 500mg/kg/day, according to histopatological testing. Conclusion: As a result, flavonoid had no harmful impact in brain and heart mice after subacute therapy up to a level of 500 mg/kg/ body weight. High doses of 1000 and 2000 mg/kg/day are not recommended for long-term use.

Sub-acute toxicity effects of &lt;i&gt;Garcinia kola&lt;/i&gt; on serum electrolytes, haematological, visceral organ weights and histopathological profiles in Wistar rats

This study was undertaken to evaluate the toxicity effects of root extract of G. kola on serum electrolyte, haematological and histological parameters of rats. Rats of both sexes were randomized into groups and orally administered daily with determined doses of G. kola extract using distilled water as a control for 21 days. On the 22nd day, all the animals were sacrificed and dissected to collect blood and selected organs. The serum and whole blood were assayed for serum electrolytes and haematological parameters respectively while selected organs were examined for their weight and histopathological lesions. The extract of G. kola did not cause significant alteration in majority of the serum electrolytes and hematological indices. However, the extract significantly elevated the mean corpuscular heamoglobin concentration. On the other hand, the extract reduced mean corpuscular volume, haematocrit (150 and 600 mg/kg), mean platelet volume (150 and 600 mg/kg) and procalcitonin (150 mg/kg). In the vital organs, there were no significant lesions observed except at the highest dose. The root extract of G. kola is relatively safe in rats when repetitively administered orally in small doses for a prolonged period of time to ensure that its use is free of toxicity to humans.

Sub-acute toxicity of Ashwagandha (Withania somnifera) root extract in wistar rats

Withania somnifera (ashwagandha, WS) is widely used in traditional Indian Ayurvedic medicine. Studies indicate ashwagandha possesses antioxidant, anxiolytic, memory enhancing, antiparkinsonian, anti-venom, anti-inflammatory and antitumor properties. Present study evaluated the sub-acute toxicity of repeated dose administration of Ashwagandha root extract in wistar rats. Material and methodsSub-acute toxicity of Ashwagandha was done as per the OECD-407 guidelines and was carried out for 28 days where satellite group was observed for 43 days. Wistar rats, 30 male and 30 females, were included in the study with 10 [5 M, 5 F] animals per group. Laboratory procedures were performed in accordance with CPCSEA guidelines. Animals were housed in standard laboratory conditions and were administered drugs orally- vehicle to control group and Ashwagandha 200, 400, 800 mg/kg body weight/day to study group. General parameters were noted, blood collection was done for haematological and biochemical parameters. All the animals were sacrificed, dissected and observed for gross necropsy and organs of high dose groups from control and Ashwagandha groups were sent for Histopathological examination. ResultGradual weight gain was observed in all the animals. No signs of intoxication and no changes in blood biochemistry were observed. Histopathological changes in organs were within normal limits. ConclusionAfter repeated dose administration, Ashwagandha root powder extract did not show any major abnormality in a dose 5 times of the recommended human dose and above upto 800 mg/kg.

Acute and 28-day toxicity evaluation of hydroethanolic extract of &lt;i&gt;Eragrostis tremula&lt;/i&gt; (Poaceae) in Wistar rats

Eragrostis tremula is utilized in Nigeria and other African countries as a memory enhancer, lactation stimulant, antiemetic, aphrodisiac and remedy for snake bites. Scientific reports revealed that this plant has anti-oxidant, anticholinesterase, cytotoxic and memory enhancing properties; despite these potentials, there is paucity of safety data to support its continued usage. This study investigated the toxicity profile of hydroethanolic extract of E. tremula (HEET) in Wistar rats. Acute and sub-acute (28 days at doses of 250, 500 and 1000 mg/kg per oral) toxicity tests were conducted using OECD 425 and 407 guidelines respectively. Limit test at 5,000 mg/kg was conducted to ascertain the midpoint lethal dose (LD50). The LD50 of HEET was above 5000 mg/kg per oral and no significant alterations in haematological parameters and tissue morphology were observed. In the sub-acute study, no death was recorded. There were no changes in food intake, organ/body weight, lipid profile, liver and renal function indices. However, histology of the kidneys showed slight tubular adhesion and glomerular necrosis. HEET was practically safe after acute administration with no practical deleterious effect at 250 mg/kg after prolonged administration in rats. However, 28 days administration of high doses caused slight kidney injury.

Safety evaluation of standardized Ayurvedic formulation-Panchvalkala, by subacute toxicity study

Ethnopharmacological relevancePanchvalkala is a conventional Ayurvedic medicine used as a douche in gynecological disorders such as leucorrhea, infertility, and endometriosis. Recently, we have reported the anticancer activity of Panchvalkala aqueous extract (PVaq) in cervical cancer cell lines, SiHa (HPV16+), HeLa (HPV18+), and mouse papilloma models. Aim of the studyHere, we have evaluated the safety of the aqueous extract of Ayurvedic formulation, Panchvalkala (PVaq), in Swiss albino mice by performing subacute toxicity study. Materials and methodsMale and female Swiss albino mice (n = 5/sex/group) were gavaged orally with different doses of PVaq for 28 consecutive days. The mice were distributed into six groups: I (vehicle control), II (vehicle control reversal), III (PVaq 250 mg/kg), IV (PVaq 500 mg/kg), V (1000 mg/kg) and VI (1000 mg/kg high dose reversal). Animals were observed periodically to record any clinical signs of toxicity or mortality. After completion of treatment and recovery periods, animals were evaluated for the effect of PVaq on urine parameters, followed by hematological and biochemical parameters. Animals were sacrificed on day 29 for gross observation of vital organs and to study their histopathology. Reversal groups were maintained for further 14 days to observe any delayed onset of toxic side effects or reversal of toxicity, followed by sacrificing the mice on day 43. ResultsIn the subacute toxicity study, PVaq did not show any significant change in food, water consumption, and body weights. There were no significant alterations in hematology, biochemistry, urine parameters, and histopathology of the analyzed tissues (brain, heart, liver, lung, spleen, thymus, kidney, epididymis/ovaries, and testis/uterus). The parameters were comparable to their respective controls in both the female as well as the male mice groups. Upon macroscopic and microscopic observation of vital organs, no abnormality was detected compared to the respective control groups. ConclusionThe subacute toxicity study demonstrated that oral administration of PVaq was safe in female and male Swiss albino mice.

Assessment of cytotoxicity, acute, subacute toxicities and antioxidant activities (in vitro) of Sanghuangporus vaninii crude polysaccharide

Ethnopharmacology relevanceSanghuangporus vaninii (S. vaninii), as a traditional large medicinal fungus, has a history of more than 2000 years in Chinese history and has been widely used to treat female diseases such as vaginal discharge, amenorrhea, and uterine bleeding, and recent pharmacological studies have also found that it has antioxidant, anti-inflammatory, and anti-tumor physiological activity, which has received more and more attention. Aim of the studyThe objective was to evaluate cytotoxicity and the acute, subacute toxicity, and in vitro antioxidant activity of S. vaninii crude polysaccharide (SVP). Materials and methodsThe monosaccharide composition of SVP was determined by HPLC (high-performance liquid chromatography). The cytotoxicity of different concentrations of SVP on three types of cells (HT-22, Kupffer macrophages, HEK293) was assessed using CCk-8. The acute toxicity in vivo was evaluated for 14 days after the administration of SVP (2500,5000, or 10,000 mg/mL). For the evaluation of subacute toxicity, mice were daily treated for 28 days with SVP (2500,5000, or 10,000 mg/mL). In addition, DPPH, hydroxyl radical, and superoxide anion radical were used to evaluate the in vitro antioxidant activity of SVP. ResultsSVP was not toxic in all three cell lines tested. In vitro antioxidant tests on the extracts showed that SVP possessed a strong antioxidant capacity in vitro. In the acute study, the no-observed-adverse-effect level (NOAEL) in male and female rats was 10，000 mg/kg body weight. There were also no deaths or severe toxicity associated with SVP in subacute studies. However, SVP treatment had a decreasing effect on body weight in mice of both sexes (2500, 5000, and 10000 mg/kg). At doses (5000 and 10,000 mg/kg), SVP had a reduced effect on food intake in both male and female mice. In addition, there were significant effects on organ coefficients of the liver, lung, and kidney. Hematological analysis showed significantly lower LYM (%) values in mice of both sexes, with significantly lower MCH (pg) values obtained in males (5000 mg/kg and 10000 mg/kg) and higher GRAN (%) values in females. In addition, the RDW-SD (fL) values were significantly lower in the male mice given the highest dose. Biochemical tests showed that there were no significant changes in ALT, AST, TP, and Cr levels after SVP treatment. In histopathological analysis, mild liver toxicity was observed in both female mice treated with 10,000 mg/kg SVP. ConclusionThe extract of SVP showed a predominance of polysaccharide compounds, with non-toxic action in vivo. Our approach revealed SVP on the chemical composition and suggests a high margin of safety in the popular use of medicinal fungi. In conclusion, our results suggest that SVP is safe, and can be used as health care products and food.

Phenolic profile, acute and subacute oral toxicity of the aqueous extract from Moroccan Mentha longifolia L. aerial part in Swiss Albino mice model

Ethnopharmacological relevanceMentha longifolia (L.) (Lamiaceae) is a native plant in Morocco, traditionally used in different countries to treat several disorders notably gastrointestinal illnesses, respiratory disorders, infectious diseases, inflammatory diseases, and menstrual problems. Robust scientific evidence has confirmed multiple pharmacological properties of M. longifolia including antihemolytic, anti-inflammatory, antibacterial, hepatoprotective, anti-cancer, antidiabetic, gastroprotective effect, and antispasmodic activity. Aim of the studyThe current study aimed to determine the phytochemical profile and assess the toxic effect of an aqueous extract of the arial parts of M. longifolia in male and female Swiss albino mice during acute and subacute oral toxicity. Materials and methodsHigh-performance Liquid Chromatography Diode Array Detector (HPLC-DAD) was used to provide qualitative and quantitative analyses of phenolic compounds of M. longifolia aqueous extract. In acute toxicity experiments, four distinct groups of mice (n = 5/group/sex) were administered Mentha longifolia aqueous extract at single oral dosages of 0.5; 1; 2; 4, and 8 g/kg BW given by gavage and intraperitoneal for up to 14 days. Regarding the subacute toxicity investigation, Swiss albino mice were given M. longifolia aqueous extract orally at dosages of 100; 500; and 1000 mg/kg BW daily for 28 days. Body weight is measured every 7 days and suggested biochemical and hematological parameters were quantified, at the finish of 28 days of daily administration, sections of the liver, kidney, and spleen were histologically evaluated for showing damage to organs. ResultsThe data of High-performance Liquid chromatography analysis revealed that M. longifolia aqueous extract was rich in interesting phytochemical compounds, mainly quercetin, and rutin, followed by a hydroxybenzoic acid-like syringic acid. Regarding the acute test in mice, no mortality or symptoms of toxicity were detected following oral administration with a single dose of M. longifolia aqueous extract at any dosage limit up to 4 g/kg, which was the no-observed side effect threshold (NOAEL). The mortality rate as well as acute toxicity of the M. longifolia aqueous extract delivered intraperitoneally, are increased progressively with increasing dosage. The non-observed adverse effect level (NOAEL) for the intraperitoneal dosage was 1 g/kg BW, and the lowest observed adverse effect level (LOAEL) was 2 g/kg BW, the estimated acute toxicity (LD50) of intraperitoneally given M. longifolia aqueous extract in mice was 4.800 g/kg BW. Concerning subacute examinations in mice, the M. longifolia aqueous extract did not induce substantial modifications in biochemical or hematological indicators, preserving a slight increase in creatinine and urea levels. At the end of the experiment, a histopathological examination of the kidneys, liver, and spleen revealed normal architecture, suggesting no morphological damage. ConclusionThe data we obtained indicate that acute or subacute administration of Mentha longifolia aqueous extract is relatively non-toxic in male and female Swiss albino mice.

Acute and 28-Day Repeated-Dose Oral Toxicity of the Herbal Formula Guixiong Yimu San in Mice and Sprague-Dawley Rats.

To evaluate the acute and chronic 28-day repeated-dose oral toxicity of Guixiong Yimu San (GYS) in mice and rats, high-performance liquid chromatography (HPLC) was used to determine the stachydrine hydrochloride in GYS as the quality control. In the acute toxicity trial, the mice were administered orally at a dose rate of 30.0 g GYS/kg body weight (BW) three times a day. The general behavior, side effects, and death rate were noticed for 14 days following treatment. In the subacute toxicity trial, the rats were administered orally at a dose rates of30.0, 15.0, and 7.5 g GYS/kg BW once a day for 28 days. The rats were monitored every day for clinical signs and deaths; changes in body weight and relative organ weights (ROW) were recorded every week, hematological, biochemical, and pathological parameters were also examined at the end of treatment. The results showed that the level of stachydrine hydrochloride in GYS was 2.272 mg/g. In the acute toxicity trial, the maximum-tolerated dose of GYS was more than 90.0 g/kg BW, and no adverse effects or mortalities were noticed during the 14 days in the mice. At the given dose, there were no death or toxicity signs all through the 28-day subacute toxicity trial.The oral administration of GYS at a dose rate of 30.0 g/kg/day BW had no substantial effects on BW, ROW, blood hematology, gross pathology, histopathology, and biochemistry (except glucose), so 30.0 g/kg BW/day was determined as the no-observed-adverse-effect dosage.

In vivo anti-inflammatory activity, safety and gene expression profiles of Carissa edulis, Withania somnifera, Prunus africana and Rhamnus prinoides for potential management of rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a chronic, inflammatory and systemic autoimmune disease. Treatment for RA is aimed at eliminating symptoms, slowing disease progression, and optimizing quality of life. However, drugs currently in use are associated with adverse side effects. Search for alternative treatment for rheumatoid arthritis involves traditional herbal plants owing to the fewer side effects and more compatibility with long-term usage compared to the conventional drugs. The use of the selected medicinal plants to manage RA among local communities in Kenya is rife. This study sought to establish the safety and effectiveness of Carissa edulis, Withania somnifera, Prunus africana and Rhamnus prinoides aqueous extracts in the management and treatment of RA. MethodLambda IV Carrageenan was used to induce inflammation and the percentage inhibition calculated, gene expression of IL-6, TNF-α and IL-4 was evaluated using Real Time Polymerase Chain Reaction and acute oral and sub-acute toxicity was assessed in Swiss albino mice. ResultsC. edulis, W. somnifera, P. africana and R. prinoides showed a dose dependent anti-inflammatory activity, there was also a downregulation of TNF-α and IL-6 and upregulation expression of IL-4. Acute toxicity showed no mortality or significant changes in body weight and behavioral parameters at a cut-off dosage of 2000 mg/kg of the plant's extracts. The sub-acute toxicity also confirmed no toxic effects as evidenced by the hematological parameters and weekly change in body weights of mice. ConclusionThis study confirms potential application of these medicinal plants in RA management and act as a lead in drug development.

Evaluation of the Antibacterial Activity and Toxicity Properties of Funtumia elastica (Preuss) Stapf. (TSN 30176), Used in Traditional Medicine in Nigeria

Background: The urgent need for new and novel antibacterial chemotherapy to combat the worrisome emergence of antimicrobial resistance necessitated the exploration of medicinal plants such as Funtumia elastica. This study was designed to evaluate the antibacterial activity, acute and sub-acute toxicity studies of Funtumia elastica which is used in the ethnomedical treatment of infections.&#x0D; Methods: The leaves and stem bark of F. elastica were collected, pulverized, extracted using soxhlet extractor and evaluated phytochemically. Antibacterial activities and Minimum Inhibitory Concentrations (MIC) of the crude extracts were investigated on clinical isolates using agar well diffusion. Bioactive fractions of the dichloromethane extract were obtained through column chromatography and thin layer chromatography. Acute and subacute toxicity studies were evaluated on the dichloromethane extract (DCM) using female Swiss albino mice.&#x0D; Results: The leaves contain tannins, flavonoids, alkaloids, steroids, saponins, and glycosides while the stem contains tannins and steroids. The hexane extracts lack activities while DCM and ethylacetate extracts of F. elastica were found to have some degree of activities on tested clinical isolates. Bioactivity guided fractionation of the DCM extract yielded only fraction 2 been active on the clinical isolates at 3.5625mg/mL. There were no signs of acute toxicity at the maximum dose of 5000mg/kg body weight. Biochemical parameters showed no significant changes in the liver enzymes. This infers that the extract might not have any negative impact on the liver with regards to metabolism.&#x0D; Conclusion: The moderate antibacterial activities of Funtumia elastica extracts justified its ethnomedicinal uses and potential to furnish new antimicrobials.

Safety assessment of European cranberrybush (Viburnum opulus L.) fruit juice: Acute and subacute oral toxicity

European cranberrybush (ECB) (Viburnum opulus L.) fruits are abundant in phenolic compounds associated with various health benefits. However, the toxicity and safety of ECB juice have not been systematically studied. In the present study, acute and subacute oral toxicities of ECB fruit juice were evaluated on Sprague-Dawley rats and BALB/c mice to establish a toxicity profile. In acute tests, a single administration of 2000 mg/kg body weight of extract to rats exhibited no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) was over 2000 mg/kg. In subacute tests, repeated administration for 28 days at 0 (control), 500, and 2000 mg/kg doses of extract in mice did not display adverse clinical signs or deaths. However, in the 2000 mg/kg subacute group, platelet counts were significantly high, which correlated with histopathological analyses revealing that ECB extract at 2000 mg/kg was toxic to the kidney, liver, and adipose tissue. The NOAEL value of ECB extract was found as 500 mg/kg/day, but further sub-chronic and chronic toxicity studies are warranted to comprehensively evaluate the long-term safety implications. The study's results emphasize the importance of considering the dosage of dietary supplements containing high levels of phenolic compounds over an extended period to avoid potential cumulative effects from prolonged consumption of high doses.

Determination of the Toxicity and Sensitizing effect of a Therapeutic Probiotic agent against Intestinal and Concomitant human infections

Studies were conducted on the toxicity and possible sensitizing effect of the lyophilizate of a therapeutic probiotic agent from the most active strains of lactic acid and propionic acid bacteria isolated from healthy people: L. plantarum 2v/A-6+L. brevis B-3/A-26+L. acidophilus 27w/60+P. shermanii 8. Based on the studies conducted to evaluate acute toxicity with an oral single administration of probiotic agent solutions (lyophilizate of lactic acid and propionic acid bacteria) at doses of 300, 2,000, 4,000, and 5,001mg/kg of weight, the toxicity class of the preparation under study has been defined as a non-toxic substance. In the study on laboratory mice of subchronic (subacute) toxicity of probiotic agent (lyophilizate of lactic acid and propionic acid bacteria)) in doses of 5.0×106, 10.0×106, and 15.0×106 CFU, it has been found that the preparation does not have a toxic effect on the body in case of 28-day use. Studies of the chronic toxicity of the probiotic agent (lyophilizate of lactic acid and propionic acid bacteria) in doses of 5.0×106, 10.0×106, and 15.0×106 CFU, in laboratory mice have shown that this preparation does not have a toxic effect on the body in case of prolonged 60-day use and does not cause structural changes in internal organs. It has been established that the therapeutic probiotic agent (lyophilizate of lactic acid and propionic acid bacteria) does not have a potential sensitizing (allergenic) effect on rat peritoneal mast cells.