The recent amendments notified by the Government of India, for conducting clinical trial, is greatly appreciable as promoting safety and well-being of human subjects. These rules clearly state that medical management of injuries in clinical trials is mandatory, and clinical trial-related injury or death needs to be compensated over and above the medical management. These rules need to be reconsidered for simplification and better understanding of issues regarding compensation. There is a need of clarity at some points which should be discussed with all stakeholders for better understanding of current regulations. In our view, attention must also be given to academic investigators, during discussion to promote availability of cost-effective treatment in India.

Aim Habb‐e‐Azaraqi (HAZ) is a compound Unani formulation used clinically since decades for the management of Laqwa (facial palsy), Fālij (paralysis), Niqris (gout) and Waja'al‐Mafāsil (arthritis). The explicit nature of HAZ i.e., Muqawwi‐i‐A'sāb (nervine tonic), Muharrik‐i‐A'sāb (nervine stimulant) rationalizes its use in nervine disorders. The main ingredient of HAZ is Azaraqi/Kuchla (Strychnos nux‐vomica L.), which is considered to be toxic in nature. Methods Acute and repeated‐dose 90‐day toxicity studies were performed as per OECD Guidelines 425 and 408, respectively. The acute toxicity study was performed at limit dose, i.e. 2000 mg/kg. The repeated‐dose toxicity study was performed at the dose levels of 100, 500 and 1000 mg/kg bw/day. Clinical signs of toxicity, body weight, and feed consumption were recorded periodically. Blood samples were subjected to hematology and clinical chemistry evaluation followed up with gross pathology and histological examinations. Results No significant differences were observed in HAZ‐treated animals with respect to body weight gain, feed consumption, hematology, or clinical biochemistry as compared to control animals. There were no significant gross pathological observations between control and drug‐treated rats. A few histopathological changes were observed in the kidney of control and HAZ‐treated animals. Conclusion No treatment‐related toxicologically significant changes were observed up to the highest tested dose except a few histopathological observations in the kidney in the high‐dose HAZ group as well as in the vehicle and satellite control groups. Data of the present study support that the traditional detoxification process effectively minimizes toxic effects of nux‐vomica used in HAZ.

Majoon-e-Nisyan (MJN) is a polyherbal semisolid compound formulation. Its description is present in various Unani literatures. It is used in Unani medicine for its therapeutic efficacy against amnesia. There is no report regarding its safety on long term administration. Therefore, toxicological evaluation of MJN is carried out in rats. Majoon-e-Nisyan was subjected to 90-days repeated oral dose toxicity studies as per OECD guide line 408. Wistar rats were treated at three dose levels i.e., 500, 1000 and 2000 mg/kg bw and one vehicle treated group. MJN and vehicle were orally administered daily for 90 days and animal were observed for clinical signs of toxicity, mortality, body weight and feed consumption. On completion of 90-days, blood samples were collected and analyzed for hematology and biochemistry. Necropsy was performed on all survived animals and vital organs were collected and subjected to histopathology. No post dose adverse effect was reported on survival of both male and female rats after oral administration of MJN for 90 days. No incidence of mortality was reported in MJN treated male and female rats at all tested dose levels. No abnormal clinical signs were observed in MNJ treated animals at 500, 1000 and 2000 mg/kg bw as compared to animals of control group. No significant changes were observed in biochemistry, hematology and histopathological examination. No incidence of mortality, adverse changes in clinical signs of toxicity or body weight gain of rats was noted. No changes in clinical chemistry, hematology, and histopathology were observed in MJN-treated or control group. Therefore, NOAEL for MJN may be considered more than 2000 mg/kg bw in rats. Subject Classification Numbers: Pharmacology, Toxicology.

Background Cisplatin is extensively used in treating cancers, and its primary side-effect is nephrotoxicity. It accumulates in proximal convoluted tubules where it promotes cellular damage by oxidative stress, apoptosis, and inflammation, etc. In Unani medicine, Tukhm-e - Karafs (Apium graveolens L.) (TK) is mentioned in the literature to manage various kidney ailments due to its diuretic and deobstruent activities. Objective To investigate the nephroprotective effects of powder of TK in Cisplatin-induced nephrotoxicity in an animal model and to validate the Unani claim of its nephroprotective action. Material and methods In curative protocol, cisplatin (5 mg/kg body weight i.p) was administered on day one and powder of TK (500 and 1000 mg/kg p.o.) from the sixth day onwards for ten days. TK (500 and 1000 mg/kg p.o.) was given for ten days and Cisplatin (5 mg/kg body weight i.p) on day 11 in the protective model. At the end of the study, all the animals were sacrificed, and renal biochemical parameters were determined. KIM-1 level was also investigated in the kidney homogenate in conjunction with histopathological inspection of kidney tissues. Results Significant increase in serum creatinine and BUN, presence of mononuclear cell infiltration, tubular dilation and vacuolation in renal histopathology, and increased KIM-1 level confirmed the nephrotoxicity due to Cisplatin. TK's administration protects the kidney as suggested by the changes in biochemical renal function, decreased level of KIM-1, and improvement in histopathological changes. Conclusion The result advocated that TK prevented renal injury and maintained normal renal function in both models. It may be due to improved clearance of Cisplatin from kidney tubules and reduction in reactive oxygen species (ROS) produced by the inflammatory response.

Background: Majoon-e-Kundur (MK) is a compound Unani formulation used in Taqteer-ul-Baul (Dribbling of urine), Salasul-Baul (Urinary incontinence), Baul Filfarash (Nocturnal enuresis), Surat-e-Inzal (Premature ejaculation) and Zof-e-Masana (weakness of urinary bladder). However, toxicity studies on MK have not been carried out for its long-term use .Objective: The present study was carried out to study the 180 days repeated dose toxicity of MK in rats. Materials and methods:The study was carried out on Sprague Dawley (SD) rats of both sexes. Animals were divided into two groups (n = 15). MK was administered at a limit dose of 2000 mg/kg bw/day p.o. for 180 days. After completion of 180 days blood samples were collected for hematological and biochemical analysis and animals were sacrificed, and organs were harvested for relative organ weight determination followed by histopathological evaluation.Results: Animals in groups treated with MK did not show any abnormal behavior or clinical signs indicative of systemic toxicity. There was no toxicologically significant alteration observed in body weight, feed intake, hematological and biochemical parameters, relative organ weights and histopathological findings of control and MK treated rats of either sex. Conclusion:There were no toxicologically significant alterations with respect to clinical signs of toxicity, body weight gain and feed intake, hematology, clinical chemistry, organ weight, gross necropsy and histopathological findings in MK treated rats at a dose of 2000 mg/kg bw as compared to control group. It may be concluded based on the above observations that MK is safe up to the limit dose tested in rats.

Qurs Afsanteen Saghir is a polyherbal Unani formulation in the form of tablet. This formulation consists of multiple medicinal plants like Afsanteen (Artemisia absinthium L.), Badam Talkh (Prunus dulcis (Mill.) D.A.Webb), Asaroon (Asarum europaeum L.), Anisoon (Pimpinella anisum L.) and Tukhm-e-Karafs (Apium graveolens L.). The clinical adult dose of study drug is 3.5 –7 g per day as mentioned in Unani literature. The present study evaluated the antipyretic, analgesic and anti-inflammatory potential of Qurs Afsanteen Saghir using different animal models. Antipyretic activity was measured using yeast-induced pyrexia model in rats at 360 and 720 mg/kg bw dose of test drug and paracetamol (70 mg/kg bw p.o.) as standard control. Analgesic effect was evaluated using acetic acid-induced writhing test in mice using test drug at dose 720 and 1440 mg/kg bw and diclofenac sodium (15 mg/kg bw p.o.) as standard control. Eddy’s hot plate test was conducted in rats using test drug at the dose of 360 and 720 mg/kg bw and buprenorphine (0.10 mg/kg s.q.) as standard control. Anti-inflammatory activity was assessed by carrageenan-induced paw edema model in rats with the dose of 360 and 720 mg/kg of test drug and Indomethacin (10 mg/kg p.o.) as standard control. The study drug significantly reduced the temperature and pain at both dose levels in a time-dependent manner as compared to normal control. However, the reduction of inflammation was observed at low dose (360 mg/kg bw) only after 3 hours of carrageenan administration. These findings indicated that tested drug showed potential activity as antipyretic and analgesic; whereas the drug may not be considered quite effective as an anti-inflammatory agents.

The ultra-fine powder of Sang-e-Surma (Surma Stone), also known as Kohl, is used for various eye ailments either alone or in combination with other herbal or mineral ingredients. The earliest use of Surma is reported in Egypt about 3100 BC. Data from a number of studies conducted on Sang-e-Surma using modern analytical techniques have cleared the uncertainty that Surma stone is mainly composed of lead sulphide. Surma is reported to be used for impaired eye-sight, ophthalmia, cataract, itching, redness, irritation, watering of eyes, shedding of eyelashes and in the initial stage of cataract. The use of lead based Surma is discouraged owing to reports of lead toxicity though the sun glare protection and antimicrobial effects of Surma have been established. Reports on lead toxicity by the application of Surma in eyes are conflicting. Appropriately planned studies are warranted to elaborate the toxic effects of lead based Surma/kohl in terms of detoxification of Sang-e-Surma, preclinical toxicity and clinical trial.

Background: Majoon Najah is a polyherbal traditional Unani formulation recommended for the treatment of neurological disorders. To evaluate antiepileptic and antidepressant activity of majoon najah and majoon najah extract in experimental animals. Methods: Anticonvulsant activity was tested using maximal electroshock induced convulsion in male sprague dawley rats using diazepam 3 mg/kg, p.o. as positive control. Pentylenetetrazole induced convulsion in swiss male albino mice was performed using phenytoin 25 mg/kg i.p. as positive control. The antidepressant activity of MN was evaluated using forced swim test model in male using Imipramine 20 mg/kg, p.o. as positive control. Results: Antiepileptic study data showed reduction of all parameters like, tonic hind limb extension, clonic convulsion and stupor; however the values were not found statistically significant at all tested dose levels. The results of forced swim test model indicated that majoon najah effectively showed significant (P<0.001) reduction in immobility duration in animals treated with majoon najah classical at dose 500 mg/kg bw and 1000 mg/kg bw as compared to control rats. Conclusion: Based on above findings, it may be concluded that majoon najah did not showed effectiveness in epilepsy however, the results evident that majoon najah is a potential Unani formulation having antidepressant activity which may be preferred as an alternative therapy over modern medicine to treat depression.