SAFETY OF HERBAL DRUGS

The quality and efficacy of treatment in the healthcare industry have dramatically changed over the last century as a consequence of advancements in medical science, mass manufacturing of chemically synthesized pharmaceuticals, and technologies. However, due to the fact that natural treatments are more accessible but also less expensive than prescribed medicines, significant percentages of the population preferring to use herbal medicine for their primary care. Furthermore, it is believed to be more natural and safer than pharmaceutical medications. Additionally, the demand for herbal treatments has been growing globally in recent years as a result of medicinal plants' gaining popularity and use. Different biological activity could be identified in herbal extracts and for active constituents. Many disorders, including diabetes, autoimmune disorders, cancer, asthma, allergies, epilepsy, and Alzheimer's disease, are effectively treated with medicinal herbs. It is believed that plants are used to make 25% of conventional medications. Aspirin, artemisinin, ephedrine, and paclitaxel are the examples of first used medicines [1]. In response to rising demand, several well-known pharmaceutical firms are doing research on the development of herbal supplements with varied biological activities. By 2027, the global herbal supplements industry is expected to reach 119.9 billion US dollars [2]. According to the World Health Organization, herbal medications are used by 80% of the world's population [3]. Despite the fact that herbal remedies are generally recognized as safe and effective, many publications about side effects, adverse effects, and adverse reactions are associated with the use of herbal medicines highlighted that “as the use of herbal medicines has increased, so too have the reports of suspected toxicity and adverse events” [4]. Adverse effects of herbal drugs might occur via intrinsic or extrinsic effects. The extrinsic effects are not just related to the plant itself, but are also a problem in commercial production as well as from contamination, adulteration, misidentification of plants or interactions with other herbal preparations. To identify and reduce the risk of these problems, effective identification systems and reliable methods for detecting foreign material are required for revealing quality and purity of herbal medicines. On the other hand, the intrinsic effects can be caused by herbal medication side effects, reactions occurring as a result of overdose or over duration, tolerance, dependence-addiction, hypersensitivity, allergic and idiosyncratic reactions, and chronic toxic effects including liver, renal, cardiac and neurotoxicity and even genotoxicity and teratogenicity which can be life-threatening [5]. Many medicines and herbal remedies interact with each other and can harm one's health. There are also numerous publications on this topic. As an example on this subject; the main issue with using St. John's wort supplement has been reported as interaction with a variety of medications. St. John's wort's active ingredient, hyperforin, induces a variety of cytochrome P450 liver isoenzymes, including CYP3A4, CYP2E1, and CYP2C9. P-glycoprotein transport activity was inhibited in a dose- and time-dependent manner by a St. John's wort extract containing hyperforin, hypericin, and quercetin. In contrast to quercetin and hypericin, which alter transporter function through protein kinase C, St. John's wort extract and hyperforin directly reduce P-glycoprotein activity. St. John's wort can therefore interact with medications that are processed by the liver's cytochrome P450 enzymes as well as medications that are substrates for P-glycoprotein but are not metabolized by the liver, leading to treatment failure because of subtherapeutic levels of these medications. Immunosuppressants, anticoagulants, statins, calcium channel blockers, b-blockers, cardiac inotropic drugs, antiretroviral drugs, anticancer drugs, benzodiazepines, antidepressants, antiepileptic drugs, and oral contraceptives have all been related to clinically significant interactions with St. John's wort. While the majority of drug interactions involving St. John's wort are pharmacokinetic interactions that could lead to treatment failure, there have also been reports of pharmacodynamic interactions between St. John's wort and selective serotonin reuptake inhibitors like paroxetine, sertraline, venlafaxine, and nefazodone that result in central serotonin syndrome [6]. Estimations are around 1 billion $ for a single novel drug, moreover drug development is a timeconsuming process, with 12-15 years from finding a hit to the clinical application [7]. Preclinical and clinical trials must be completed before a drug marketed to the public, and the studies must confirm that the drug is safe.