Toxicological evaluation of aqueous extract of the traditional Chinese formula Qing Hao Gan Cao

Abstract Qing Hao Gan Cao (QHGC), a Chinese medicinal formula containing Artemisia annua and Glycyrrhizae Radix et Rhizoma, has been used to treat sunstroke and as an antiviral agent for more than 800 years. It has not previously been subject to a toxicological safety evaluation in acute and subacute (28 days) studies. Therefore, the acute and subacute toxicity of an aqueous extract of QHGC were evaluated in vivo. For the QHGC preparation, the botanical raw materials were crushed into pieces and mixed in the ratio of 10:1 in distilled water for 12 h, then boiling three times for 2 h each time. The three decoctions were mixed and filtered, then spray-dried with hot air at 160°C for 30 min, and stored at room temperature. For the acute toxicity test, 72.0 g/kg of QHGC extract was administered by gavage to male and female mice. Body weight, general observations, and autopsy results were recorded. No mortality or toxicity signs were observed during the studies. For the subacute toxicity test, 4.0, 8.0, or 16.0 g/kg/day of QHGC extract was administered to rats for 28 days. General observations and mortality, body weight, biochemical and hematological parameters, organ weight, and pathological morphology were analyzed. The acute and subacute toxicity studies did not show significant changes in body weight, general observations, hematology and biochemical parameters, organ weight, and liver, spleen, stomach, duodenum, testis, ovary, lung, heart, and kidney histopathological analyses. The consumption of QHGC aqueous extract can be considered safe within the conditions of this study.

Download Full-text

Acute and Subacute Toxicity Studies of the Aqueous Extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by Oral Administration in Rodents

BioMed Research International ◽

10.1155/2020/4020647 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Loubna Kharchoufa ◽

Mohamed Bouhrim ◽

Noureddine Bencheikh ◽

Soufiane El Assri ◽

Asmae Amirou ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Administration ◽

Aqueous Extract ◽

Hematological Parameters ◽

Toxicity Study ◽

Toxicity Tests ◽

Potential Toxicity ◽

Histological Studies ◽

Subacute Toxicity

Ethnopharmacological Relevance. Haloxylon scoparium Pomel is a herbal medicine traditionally used for treating scorpions and snakebite, diabetes, and stomachache as well as several other diseases. No systematic study of the potential toxicity of the plant has been described. Aim of the Study. The current study is aimed at assessing the potential toxicity of Haloxylon scoparium Pomel through the acute and subacute toxicity tests. Materials and Methods. Acute toxicity test was performed on Swiss albino mice at a single oral dose of 1-10 g/kg for 14 consecutive days. General behavioral adverse effects, mortality, and latency of mortality were determined. In the subacute study, the Haloxylon scoparium Pomel extract was administered orally at doses of 500, 1000, and 2000 mg/kg daily for 30 days to Wistar rats. Body weight and selected biochemical and hematological parameters were determined at the end of the experiment. Sections of livers and kidneys were removed for histological studies. Results. Acute toxicity study showed that the oral LD50 value of Haloxylon scoparium Pomel extract was 5000 mg/kg. The subacute toxicity study of Haloxylon scoparium Pomel extract at doses 500, 1000, and 2000 mg/kg did not produce any observable symptoms of toxicity and no significant variation in body weight, organ weights, food, and water consumption or mortality in all treated rats. However, the administration of the Haloxylon scoparium Pomel extract to rats at 500 mg/kg and 1000 mg/kg showed a significant decrease in platelets. Moreover, only at the highest dose (2000 mg/kg), the extract caused a significant increase in red blood cells and hemoglobin. Our results showed that subacute treatments with Haloxylon scoparium Pomel extract at doses of 1000 mg/kg and 2000 mg/kg significantly elevated alkaline phosphatase and triglycerides. Histological studies showed that the subacute treatments of rats with Haloxylon scoparium Pomel extracts, at the doses 1000 and 2000 mg/kg, induced some histopathological changes in the livers but a slight changing in kidneys. Conclusion. Our results indicated low acute toxicity of the aqueous extract of Haloxylon scoparium Pomel. Furthermore, daily oral administration of Haloxylon scoparium Pomel extract caused some damages to the livers of rats treated with high doses, expressed by an increase in some enzyme activities such as ALP. Regarding the renal function, we did not find remarkable toxicity in the subacute treatment with Haloxylon scoparium Pomel extracts at doses 1000 and 2000 mg/kg. However, further toxicity assessments should be done to ascertain the safety or the toxicity of this valuable plant species “Haloxylon scoparium pomel” in subchronic treatments.

Download Full-text

In vitro and in vivo toxicity assessment of biologically synthesized silver nanoparticles from Elaeodendron croceum

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2018-0184 ◽

2019 ◽

Vol 16 (3) ◽

Cited By ~ 6

Author(s):

S. W. Odeyemi ◽

J. De La Mare ◽

A. L. Edkins ◽

A. J. Afolayan

Keyword(s):

Silver Nanoparticles ◽

Body Weight ◽

Aqueous Extract ◽

Hematological Parameters ◽

Weight Ratio ◽

Control Group ◽

Significant Difference ◽

Glutamyl Transferase

Abstract Background The cytotoxic properties of nanoparticles have attracted a great deal of attention in the field of nanoscience and nanotechnology due to their small size and ability to penetrate cellular membranes. Methods The silver nanoparticles were synthesized using Elaeodendron croceum stem bark and characterized. The oral acute toxicity studies were carried out by administration of 500, 1000, 2000 mg/kg body weight to Wister rats in respective groups. An in vitro cytotoxicity assay was evaluated in MDA-MB-231 breast cancer cells using the WST-1 Cell Proliferation assay. The percentage of cell viability after treatment with aqueous extracts of Elaeodendron croceum (ECE) and Elaeodendron croceum silver nanoparticles (ECAgNPs) was compared with that of paclitaxel. Results The in vivo studies revealed that the LD50 was higher than 2000 mg/kg and there was no significant difference (p>0.05) between the treatment groups compared with the control group for mean organ-to-body weight ratio except in the liver and in all hematological parameters except WBC and hematocrit. Similarly, there was no significant difference (p>0.05) for serum electrolytes (Na+, Mg2+ K+, Cl−, and Ca2+), total protein, urea, ɣ-glutamyl transferase (GGT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), albumin, total and conjugated bilirubin between the treatment and the control group. However, there were changes in creatinine, urea, and cholesterol. In the in vitro assays, ECE and ECAgNPs showed IC50 values of 70.87±2.99 and 138.8±3.98 µg/mL respectively against MDA-MB-231 cells compared to paclitaxel, which showed an IC50 value of 80 ng/mL. Conclusion The results showed that the LD50 of the ECE and ECAgNPs in Wister rats was determined to be greater than 2000 mg/kg body weight. The aqueous extract also showed more cytotoxic than the ECAgNPs suggesting that the toxic compounds in aqueous extract were involved in the capping of the AgNPs.

Download Full-text

In Vivo Subacute Toxicity and Antidiabetic Effect of Aqueous Extract of Nigella sativa

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8427034 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Karima Bensiameur-Touati ◽

Ghouti Kacimi ◽

El-Mehdi Haffaf ◽

Sihem Berdja ◽

Souhila Aouichat-Bouguerra

Keyword(s):

Aqueous Extract ◽

Nigella Sativa ◽

Histological Study ◽

Diabetic Rats ◽

Antidiabetic Effect ◽

Subacute Toxicity ◽

Wide Range ◽

Liver And Pancreas ◽

Liver Tbars

Context. Nigella sativa seeds are usually used as traditional medicine for a wide range of therapeutic purposes. Objective. To investigate the subacute toxicity of NS aqueous extract and select its lowest dose to study its antidiabetic effect. Methods. 5 AqE.NS doses (2, 6.4, 21, 33, and 60 g/Kg) were daily administered to mice by gavage. Biochemical parameters measurements and histological study of the liver and the kidney were performed after 6 weeks of supplementation. Thereafter, and after inducing diabetes by alloxan, rats were treated by 2 g/Kg of AqE.NS during 8 weeks. Metabolic parameters were measured on sera. A horizontal electrophoresis of plasmatic lipoprotein was conducted. Glycogen, total lipids, and triglycerides were measured in the liver. TBARS were evaluated on adipose tissue, liver, and pancreas. Results. AqE.NS showed no variation in urea and albumin at the 5 doses, but hepatotoxicity from 21 g/Kg was confirmed by histopathological observations of the liver. In diabetic rats, AqE.NS significantly decreased glycemia, TG, T-cholesterol, LDL-c, and TBARS and showed a restored insulinemia and a significant increase in HDL-c. Results on the liver indicated a decrease in lipids and a possible glycogenogenesis. Conclusion. AqE.NS showed its safety at low doses and its evident antihyperglycemic, antihyperlipidemic, and antioxidant effect.

Download Full-text

In vitro and in vivo Activities of Psidium guajava and Azadirachta indica Leaf Extracts and solvent Fractions against Salmonella Typhi

European Journal of Medicinal Plants ◽

10.9734/ejmp/2021/v32i730405 ◽

2021 ◽

pp. 56-71

Author(s):

Adetutu Adewale ◽

Olaniyi Deborah Temitope ◽

Awodugba Tamilore ◽

Owoade Abiodun Olusoji ◽

Olaniyan, Lamidi Waheed B. ◽

...

Keyword(s):

Body Weight ◽

Hematological Parameters ◽

Sub Saharan Africa ◽

Male Rats ◽

Carrier Status ◽

Leaf Extracts ◽

Salmonella Infections ◽

Neem Leaves

Typhoidal salmonella infections remain a challenge in the health care system in sub-Saharan Africa. Carrier status and advent of multi-drug resistant S. Typhi strains have necessitated the search for new drug leads. Hence, this study aims at investigating P. guajava and A. indica leaves for anti-salmonella activities. Guava and neem leaves were extracted by maceration in methanol and fractionated by solvent partitioning. In vitro activities were assessed by agar well diffusion and broth micro-dilution methods. Sixty male rats were randomized to 10 groups of 6 animals each for the in vivo experiments. Groups of rats except, normal control, were induced with 0.5McFarland of S. Typhi suspension orally. Treatment groups received 200 mg/kg body weight of extracts and fractions, and the control groups were treated with 14.29mg/kg body weight of ciprofloxacin and 1%v/v DMSO for 7 days post-infection. Biochemical parameters were determined spectrophotometrically. Hematological parameters were analyzed with automated hematology diagnostic machine. All fractions of P. guajava and three of A. indica inhibited S. Typhi growth with Zone of Inhibition (ZI) ranging from 11-15 mm. Active fractions inhibited 48.60-62.45% of S. Typhi biofilm formation at 25 mg/mL with Minimum Bactericidal Inhibitory Concentration (MBIC) of 0.39-12.5 mg/mL. All fractions improved body weight of treated rats and inhibited bacteremia at 44.75 and 95.94%. Hematological parameters improved in all fractions-treated rats. MDA was not significantly (p<0.05) altered in all groups. One fraction of P. guajava (ePg) lowered the elevated level in concentration of Nitric oxide (NO) while all fractions enhanced the lowered activity of SOD. Elevated (lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (BIL) were lowered by all fractions to various extents in treated rats. Fractions of P. guajava, and A. indica could be further considered for identification of active anti-salmonella principle(s).

Download Full-text

Preliminary Phytochemical Analysis of Aqueous Extract of Leaf Psidium guajava and Its Effect on Some Haematological Parameters

Asian Journal of Biochemistry, Genetics and Molecular Biology ◽

10.9734/ajbgmb/2021/v8i430200 ◽

2021 ◽

pp. 16-24

Author(s):

M. I. Uneze ◽

D. N. Azionu

Keyword(s):

Body Weight ◽

Aqueous Extract ◽

Hematological Parameters ◽

Research Work ◽

Psidium Guajava ◽

Albino Rats ◽

Phytochemical Analysis ◽

Standard Procedures ◽

Dose Dependent ◽

Average Body

Various parts of psidium guajava linn are used in ethnomedicine in controls and treatments of different disorders such as liver, heart, and blood related disorders [11]. This research work investigate qualitative phytochemical composition of ethanol leaf extract of psidium guajava linn and its effect on some hematological parameters in albino rats. Qualitative phytochemical analysis of the extract was performed by standard procedures. A total of 20 adult male albino rats were used, they were randomly placed into 5 groups (A, B, C, D and E) each group containing 4 rats groups A, B, C, and D were administered, via oral intubation, the extract at doses of 200, 400, 600, and 800 mg/kg body weight respectively of the extract for 7 consecutive days. Phytochemical screening shows that the extract was rich in tannins anthraquinones, and flavonoid while alkaloids, saponins, terpenes and glycoside were slightly present. There was a decrease in the average body weight, physical activities, and feed and water intake of the rats in the test groups relative to the control hemoglobin concentrate, total white blood cell and packed cell volume recorded in the groups administered the extract were significantly (p<0.05) higher than in the control this effect on the haemotological parameters was found to be dose dependent. The findings of this study suggest that the aqueous extract of the fruit plants may be useful in control and treatment of blood related disorders. These useful applications may be as a result of the phytochemical present in the extract.

Download Full-text

Acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii (Miq.) Miq. stem bark in rats

The Journal of Phytopharmacology ◽

10.31254/phyto.2021.10204 ◽

2021 ◽

Vol 10 (2) ◽

pp. 89-97

Author(s):

EL Lappa ◽

◽

C Bogning Zangueu ◽

EL Nguemfo ◽

JJ Kojom Wanche ◽

...

Keyword(s):

Body Weight ◽

Aqueous Extract ◽

Chronic Toxicity ◽

Hematological Parameters ◽

Lethal Dose ◽

Relative Weight ◽

Stem Bark ◽

The Body ◽

Female Rats ◽

Male Rats

Ficus vogelii is a medicinal plant mainly found in tropical Africa and reported to treat inflammatory complaints. This study aims to evaluate the acute and sub-chronic toxicity of the aqueous extract of Ficus vogelii stem bark in wistar rats. For acute study, aqueous extract at a single dose of 5000 mg/kg body weight was administered to female rats and observed for 14 days. In the sub-chronic study, the extract was administered daily to both sex rats at the doses of 100, 200, 400, and 600 mg/kg body weight for 28 consecutive days. Body weight was measured weekly, while hematological, biochemical, and histopathological parameters were analyzed after euthanize. Aqueous extract of Ficus vogelii at all tested doses didn’t produced any mortality or significant change on the body weight and relative weight of rats on acute and sub-chronic studies. The lethal dose 50 was estimated greater than 5000 mg/kg (DL50˃5000 mg/kg). Hematological parameters were recorded non-significant in all treated rats. Aqueous extract at 600 mg/kg significantly changed transaminases and alkaline phosphatase activities, these changes were reversible in satellites. The concentrations of bilirubin was increased at 200 and 600 mg/kg in male rats, at 100, 400 mg/kg in female rats. The levels of lipids markers didn’t changed, except the significant decrease of LDL-cholesterol. Histological examination didn’t showed any change in the architecture of the liver and kidney of rats treated compared to control. Thus aqueous extract of Ficus vogelii stem bark didn’t produced adverse effects in rats after oral acute and sub-chronic treatment.

Download Full-text

Two-Week Repeated Oral Dose Toxicity Study of Mantidis Ootheca Water Extract in C57BL/6 Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6180236 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Hye-Sun Lim ◽

Yun Soo Seo ◽

Seung Mok Ryu ◽

Byeong Cheol Moon ◽

Goya Choi ◽

...

Keyword(s):

Body Weight ◽

Clinical Signs ◽

Water Extract ◽

Serum Biochemistry ◽

Organ Weight ◽

Control Group ◽

Subacute Toxicity ◽

Significant Toxicity ◽

Pharmacological Studies ◽

Serum Biochemical

Background. Mantidis Ootheca (MO), described as the ootheca of Hierodula patellifera Serville, 1839, Tenodera angustipennis (Saussure, 1869), or Statilia maculate (Thunberg, 1784) in Korean Herbal Pharmacopoeia, is an important herbal material that has been traditionally used for treating several medical conditions including renal failure, spermatorrhea, and pediatric enuresis in Korea. Objective. The present study investigated the potential subacute toxicity of MO water extract during a 2-week repeated oral administration of doses of 0, 50, 150, or 450 mg/kg/day to C57BL/6 male mice by gavage. Methods. The following parameters were examined during the study period: mortality, clinical signs, body weight, hematology, serum biochemistry, gross findings, organ weight, and histopathology. All the mice were euthanized at the end of the treatment period. Results. No treatment-related changes in mortalities, clinical signs, body weight, gross finding, and organ weight change were detected after 14 days of oral MO extract administration. In addition, no meaningful MO extract treatment-related changes were observed in the hematological, serum biochemical, and histopathological parameters compared with the normal control group following treatment with doses of up to 450 mg/kg/day. Conclusion. Based on these findings, we concluded that treatment of mice with the water extract of MO did not result in significant toxicity and, therefore, it could be considered safe for further pharmacological studies.

Download Full-text

Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

Scientific Reports ◽

10.1038/s41598-019-52398-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Jyoti Kaushik ◽

Simran Tandon ◽

Rishi Bhardwaj ◽

Tanzeer Kaur ◽

Surinder Kumar Singla ◽

...

Keyword(s):

Body Weight ◽

Aqueous Extract ◽

Kidney Stones ◽

Wistar Rats ◽

Lethal Dose ◽

Tribulus Terrestris ◽

Oral Toxicity ◽

Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

Download Full-text

Chronic exposure to cobalt compounds — an in vivo study

Open Life Sciences ◽

10.2478/s11535-014-0334-x ◽

2014 ◽

Vol 9 (10) ◽

pp. 973-981

Author(s):

Yordanka Gluhcheva ◽

Vasil Atanasov ◽

Juliana Ivanova ◽

Ekaterina Pavlova

Keyword(s):

Body Weight ◽

Cobalt Chloride ◽

Tap Water ◽

Organ Weight ◽

Duration Of Treatment ◽

Cobalt Ions ◽

Cobalt Compounds ◽

Pregnant Mice

AbstractAn in vivo experimental model for testing the effects of long-term chronic treatment with cobalt(II) compounds — cobalt chloride (CoCl2) and cobalt-EDTA (Co-EDTA) on mice at different stages of development was optimized. Pregnant mice and their progeny were treated with daily doses of 75 or 125 mg kg−1 body weight until postnatal day 90. The compounds were dissolved in regular tap water. Mice were sacrificed on days 18, 25, 30, 45, 60 and 90 after birth, which correspond to different stages of their development. Altered organ weight indices (calculated as a ratio of organ weight to body weight) of spleen, liver and kidneys, were found depending on the type of compound used, dose, duration of treatment, and the age of the animals. The results also showed significant accumulation of cobalt ions in blood plasma, spleen, liver and kidneys of the exposed mice. More Co(II) was measured in the organs of the immature mice (day 18, 25 and 30 pnd) indicating that they were more sensitive to treatment.

Download Full-text