AKBAMAX®, 01 Jul 2021
Published on : AKABAMAX BOSPURE | Journal ListToxicol Intv.19(3); Sep-Dec 2012PMC3532773

A-90 Day Gavage Safety Assessment of Boswellia serrata in Rats

Pooja Singh, K. Mathai Chacko, M. L. Aggarwal, Binu Bhat, R. K. Khandal, Sarwat Sultana, and Binu T. Kuruvilla

PMID: 23293466 | doi: 10.4103/0971-6580.103668


Abstract. The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of the digestive system, respiratory ailments and bone-related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt..

Introduction: All experimental animals were examined, once daily, for clinical signs, symptoms, and for mortality. Detailed clinical observations (eye abnormalities and apparent functional changes) were made for each animal once before the start of dose administration and thereafter weekly till the termination of the study. The body weight of each animal was recorded before initiation (Day zero) and weekly thereafter up to the termination of the study. The body weight of each of the fasted animals was taken, to calculate the organ weight ratio just before their sacrifice. At the end of the treatment and of the recovery period, all animals were kept for fasting overnight before collecting their blood for Hematology and Clinical Chemistry examination. Blood samples were collected via orbital sinus under light CO2 anesthesia. Hematology and Clinical Chemistry parameters were determined by using Beckman Coulter hematology analyzer and Hitachi 902 Clinical Chemistry auto analyzer system, respectively. At the end of the study, all animals from each group were sacrificed for gross and histopathological examination. A detailed gross pathological examination was conducted for external surfaces and orifices. All Organs were weighed individually immediately after necropsy and they were preserved in 10% Formalin for histopathological examinations. The tissues were processed, embedded in paraffin, sectioned and stained with hematoxylin and eosinBoswellia serrata (Frankincense) is a moderate to large branching tree (growing to a height of 12 feet) found in India, Northern Africa and the Middle East. The barks of Boswellia serrata consists majorly of a gummy oleo-resin. Boswellia serrata is a natural and safe NSAID (Non-steroidal anti-inflammatory drug) used to treat a variety of health problems. The oleo resin of Boswellia serrata has been widely used in Ayurvedic medicines against various diseases that include Arthritis, Inflammation, Colitis, Asthma, Psoriasis, Hyperlipidemia, and Cancers. Boswellia serrata contains Boswellic acids (β-boswellic acid, 3-acetyl-b-boswellic acid, 11-keto-b-boswellic acid and 3-acetyl-11-keto-β-boswellic acid) oils, terpenoids and sugars. The Boswellic acids are specific, non redox inhibitors of 5-lipoxygenase without affecting 12-lipoxygenase and cyclooxygenase activities. Though some studies related to the safety profile of Boswellia serrata were reported on experimental animals as well as on primates but they were not sufficient to explain the systemic effect. The present study was conducted to establish the safety of this herb by conducting a repeated dose 90 day oral toxicity study in accordance to OECD Guideline No. 408 and WHO Guidelines.

Methods: All experimental animals were examined, once daily, for clinical signs, symptoms, and for mortality. Detailed clinical observations (eye abnormalities and apparent functional changes) were made for each animal once before the start of dose administration and thereafter weekly till the termination of the study. Bodyweight of each animal was recorded before initiation (Day zero) and weekly thereafter up to the termination of the study. The body weight of each of the fasted animals was taken, to calculate the organ weight ratio just before their sacrifice. At the end of the treatment and of the recovery period, all animals were kept for fasting overnight before collecting their blood for Hematology and Clinical Chemistry examination. Blood samples were collected via orbital sinus under light CO2 anesthesia. Hematology and Clinical Chemistry parameters were determined by using Beckman Coulter hematology analyzer and Hitachi 902 Clinical Chemistry auto analyzer system, respectively. At the end of the study, all animals from each group were sacrificed for gross and histopathological examination. A detailed gross pathological examination was conducted for external surfaces and orifices. All Organs were weighed individually immediately after necropsy and they were preserved in 10% Formalin for histopathological examinations. The tissues were processed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin.

Results and discussion: It is evident that there were no clinical signs or symptoms to indicate that the animals were adversely affected by the doses or treatment given throughout the period of the study. This observation is further supplemented by the fact that all the animals were alive at the end of the study. The results of the bodyweight of all animals during the study. There was no effect on the mean and percentile body weights of the animals of low dose and intermediate-dose groups when compared to their control counterparts, whereas, a significant decrease was observed in the body weight gain of high dose group animals. Evaluation of various hematological parameters like WBC count, RBC count, hematocrit, and platelet count of test and recovery group animals did not reveal any changes when compared with the control group animals. All the parameters fell within the normal range except Hemoglobin which shows slightly higher values in the high dose group. The Biochemical parameters like glucose, BUN, GOT, GPT, total protein, and creatinine of the test and recovery group animals were comparable to the control counterparts except for cholesterol and triglycerides which show lower values in test groups as compared to control but it was non-significant. Statistical analysis of the weights of organs like lung, liver, kidneys, ovaries, adrenals, heart, spleen, and brain did not show any deviations in the test and recovery group animals when compared to their control counterparts. Macroscopically and microscopically, no significant changes were noticed in any treated and control group animals. All the changes noticed were incidental and are common findings of the laboratory.

Conclusion: Based on the observations and results obtained from various studies, it can be said that the Boswellia serrata given to the animals did not show any mortality as well as any adverse impact on the health of animals. As reported in the literature, the metabolic rate of both male and female rats is governed by the functions of the liver. The body weight is expected to rise with time at a standard laboratory rate. Any deviations on either side i.e. increase or decrease in body weight of the animals would be ascribed to the functioning of the organs mainly the liver. A significant decrease in body weight gain was noticed in the animals of the high-dose group. The reason for this decrease might be that as Boswellia serrata is a rich source of guggulsterone, which helps in (guggulsterone) stimulating the thyroid, leading to metabolic up-regulation, an increase in thyroid efficiency, increased caloric burn, and therefore possible weight loss. This all may lead to the reduction in the biosynthesis of cholesterol and may stimulate cholesterol’s conversion to bile acids and increased fecal excretion without having any effect on the Biochemical and Hematological parameters, organ weights, and Histopathology. The exact underlying mechanism of the decreased body weight gain needs to be further clarified. From the results of hematological parameters, it is evident that all the animals were found to show higher values of hemoglobin with the treatment. This indicates that with the administration of Boswellia serrata, animals showed an improvement in major hematological parameters. Similarly, the data of cholesterol and triglyceride suggest that the functioning of the liver improved with the increasing dose of Boswellia serrata. It may be said that the Boswellia serrata acts positively for the health factors of animals both females and males. Now, it may be noted that for almost all the parameters, the trend was reversed as soon as the dosing of Boswellia serrata was stopped. This can be understood from the values of critical parameters which were found to be similar to the ones observed for control animals. This can therefore be said that the effect of dosing the animals with the Boswellia serrata is reversible and the animal starts to exhibit similar parameters of health as observed with the control animals, once the treatment is over.

As there was a decrease in the body weight gain of the animals of high dose group (1000 mg/kg B. wt.), therefore it may be concluded that the NOAEL i.e. No observed Adverse Effect Level of Boswellia serrata came out as 500 mg/kg B. wt. /day since no reduction in the body weight gain was observed at 100 and 500 mg/kg B. wt


Keywords

  • Boswellia serrata
  • NOAEL
  • safety
  • sub-chronic
  • toxicity

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