Thymoquinone (2-methyl-5-isopropyl-1, 4-benzoquinone-TQ) is chemically a monoterpene extracted from Nigella sativa L. seed oil (Ranunculaceae) commonly known as black cumin seed. The rigorous studies have revealed that thymoquinone the major active constituent of Nigella sativa oil brings to bear majority of pharmacological actions such as anti-inflammatory, anti-oxidant, anti-diabetic and organ-protective activities. Thymoquinone is a potent phytochemical with confirmed in-vitro efficacy used for several treatment purposes. The vast studies have revealed diverse molecular pathways of nearly all major diseases. Belonging to a phytochemical group, TQ is observed as strong lipophilic constituent hence insolubility in aqueous fluids hamper its systemic bioavailability. Hence, the physiochemical parameters and the associated toxicities are the barrier for the researchers using TQ clinically. Further studies revealed that TQ is highly light and heat sensitive, which obstruct the successful formulation for the delivery of drug. The present review aims to provide insights regarding the characteristics, pharmacokinetics and targets associated with the use of TQ in different pharmacological actions. It also suggests methods to improve the use of TQ by overcoming the associated physiochemical obstacles and the related toxicities and best utilisation for animal as well as clinical studies. According to the published reports of TQ, we suggest in-depth studies regarding the bioavailability and toxicity studies in animals as well as in humans.

α-Bisabolol is one of the important monocyclic sesquiterpenes, derived naturally from essential oils of many edible and ornamental plants. It was first obtained from Matricaria chamomilla, commonly known as chamomile or German chamomile. The available literature indicates that this plant along with other α-Bisabolol containing plants is popularly used in traditional medicine for potential health benefits and general wellbeing. Nutritional studies are indicative of the health benefits of α-Bisabolol. Numerous experimental studies demonstrated pharmacological properties of α-Bisabolol including anticancer, antinociceptive, neuroprotective, cardioprotective, and antimicrobial. This review aims to collectively present different pharmacological activities based on both in vitro and in vivo studies. In the present review using synoptic tables and figures, we comprehensively present that α-Bisabolol possesses therapeutic and protective activities, therefore, it can be used for potential health benefits based on pharmacological effects, underlying molecular mechanism, and favorable pharmaceutical properties. Based on the studies mostly performed on cell lines or animal models, it is evident that α-Bisabolol may be a promising nutraceutical and phytomedicine to target aberrant biological mechanisms which result in altered physiological processes and various ailments. Given the polypharmacological effects and pleiotropic properties, along with favorable pharmacokinetics, and dietary availability and safety, α-Bisabolol can be used as a dietary agent, nutraceutical or phytopharmaceutical agent or as an adjuvant with currently available modern medicines. The regulatory approval of this molecule for use as food additives, and in cosmetics and fragrance industry is also supportive of its human usage. Moreover, further studies are necessary to address pharmaceutical, pharmacological, and toxicological aspects before clinical or nutritional usage in humans. The biological actions and health benefits open opportunities for pharmaceutical development with pharmacological basis of its use in future therapeutics.

Acetaminophen (APAP), which is also known as paracetamol or N-acetyl-p-aminophenol is a safe and potent drug for fever, pain and inflammation when used at its normal therapeutic doses. It is available as over-the-counter drug and used by all the age groups. The overdose results in acute liver failure that often requires liver transplantation. Current clinical therapy for APAP-induced liver toxicity is the administration of N-acetyl-cysteine (NAC), a sulphydryl compound an approved drug which acts by replenishing cellular glutathione (GSH) stores in the liver. Over the past five decades, several studies indicate that the safety and efficacy of herbal extracts or plant derived compounds that are used either as monotherapy or as an adjunct therapy along with conventional medicines for hepatotoxicity have shown favorable responses. Phytochemicals mitigate necrotic cell death and protect against APAP-induced liver toxicityby restoring cellular antioxidant defense system, limiting oxidative stress and subsequently protecting mitochondrial dysfunction and inflammation. Recent experimental evidences indicat that these phytochemicals also regulate differential gene expression to modulate various cellular pathways that are implicated in cellular protection. Therefore, in this review, we highlight the role of the phytochemicals, which are shown to be efficacious in clinically relevant APAP-induced hepatotoxicity experimental models. In this review, we have made comprehensive attempt to delineate the molecular mechanism and the cellular targets that are modulated by the phytochemicals to mediate the cytoprotective effect against APAP-induced hepatotoxicity. In this review, we have also defined the challenges and scope of phytochemicals to be developed as drugs to target APAP-induced hepatotoxicity.

The present study investigated the effect of hesperidin, a natural flavonoid, in cardiac ischemia and reperfusion (I/R) injury in diabetic rats. Male Wistar rats with diabetes were divided into five groups and were orally administered saline once daily (IR-sham and IR-control), Hesperidin (100 mg/kg/day; IR-Hesperidin), GW9962 (PPAR-γ receptor antagonist), or combination of both for 14 days. On the 15^th day, in the IR-control and IR-treatment groups, rats were subjected to left anterior descending (LAD) coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical, histopathological, ultrastructural and immunohistochemistry. In the IR-control group, significant ventricular dysfunctions were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in cardiac injury markers lactate dehydrogenase activity, CK-MB and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and TNF-α were observed. Hesperidin pretreatment significantly improved mean arterial pressure, reduced left ventricular end-diastolic pressure, and improved both inotropic and lusitropic function of the heart (+LVdP/dt and –LVdP/dt) as compared to IR-control. Furthermore, hesperidin treatment significantly decreased the level of thiobarbituric acid reactive substances and reversed the activity of lactate dehydrogenase towards normal value. Hesperidin showed anti-apoptotic effects by upregulating Bcl-2 protein and decreasing Bax protein expression. Additionally, histopathological and ultrastructural studies reconfirmed the protective action of hesperidin. On the other hand, GW9662, selective PPAR-γ receptor antagonist, produced opposite effects and attenuated the hesperidin induced improvements. The study for the first time evidence the involvement of PPAR-γ pathway in the cardioprotective activity of hesperidin in I/R model in rats.

Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities.