Therapeutic Insights into Herbal Medicine through the Use of Phytomolecules

Historically, natural products, which are substances generated by living organisms found in nature, have made an important contribution to pharmacotherapy, especially those from plant sources. Phloroglucinols are significant bioactive polyphenolic compounds that are found in plants, marine and microbial sources. Their chemical structures include an aromatic phenyl ring with three hydroxyl groups and are usually made of two or more rings linked together through methylene bridges. They exist widely in several plant families and are known for their significant biological potentials, such as antibacterial, antifungal, anti-inflammatory, antileishmanial, antiplasmodial, antiproliferative and cytotoxicity activities. This book chapter provides an overview of phloroglucinol compounds in the world, their location in the plant, and their pharmacological applications.

Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disease manifested by progressive articular and extra-articular disabilities. Pieces of evidence hint that tremendous research efforts have increased the likelihood of attaining a better treatment goal. However, the associated risks, drug failures, and high costs of the available drugs or regimens still limit their widespread use. Even though natural products are rarely considered for lead identification, which is counterintuitive to traditional drug development, natural products occupy a large chemical space, unlike synthetic screening methods. Although skepticism towards the use of natural products continues, the growing attention of researchers towards the diverse flora has led a plethora of molecules and therapies to reach clinical trial settings. This chapter sheds light on the challenges in the development of plant-derived compounds or therapies for the management of RA. It discusses the plant-derived products (including diet-based therapies) undergoing clinical development for the treatment of RA.

Herbal medicines are gaining popularity in the modern world for their ability to treat a wide range of ailments while having fewer side effects and greater therapeutic properties. However, there are many limitations when it comes to delivering active phytomolecules to the target site, including solubility of ingredients, susceptibility to degradation in the presence of gastric and colonic acidity, diminished metabolic efficacy attributable to gut microflora, inadequate absorption across the intestinal epithelium, suboptimal active efflux mechanisms, and susceptibility to first-pass metabolism. As a result, medication concentrations in the blood are below therapeutic levels, resulting in reduced or no therapeutic impact. With the rising popularity and potential therapies of herbal medicines over the last several decades, there has been a lot of attention paid to the new drug delivery method of active phytomolecules. Novel herbal drug carriers treat certain diseases by precisely targeting the diseased zone within a patient's body and delivering the medication there. Novel drug delivery systems have the benefit of administering herbal medicines at a preset rate and at the site of action, reducing adverse effects and increasing drug bioavailability. Controlling drug distribution in new drug delivery technology is accomplished by integrating the drug into a carrier system or altering the drug's structure at the molecular level. The integration of herbal drugs into the delivery system facilitates improvements in solubility, stability enhancement, toxicity mitigation, potentiation of pharmacological activity, optimized distribution among tissue macrophages, sustained release kinetics, and protection against physical and chemical degradation, thereby aligning with key principles in pharmaceutical formulation. The purpose of this chapter is to offer an overview of several forms of novel drug delivery systems that incorporate active components, as well as their potential therapeutic and clinical benefit.

Herbs have been an integral part of human life for ages. Modern allopathic drugs had an upper hand over traditional medicine in the past century due to their mounting inefficacy, resistance, cost, and adverse effects that have led to the reclaim of herbs once again. Herbs holistically confer biological activity due to the presence of phytochemicals, which are classified broadly as carbohydrates, lipids, terpenoids, alkaloids, polyphenols, and essential and volatile oils. In this, polyphenols are a vast group further comprising flavonoids, phenolic acid, stilbenoids, tannins, lignans, xanthones, quinones, coumarins, phenylpropanoids, and benzofurans. Of this, flavonoids are hydroxylated phenolic substances with basic C6-C3-C6 rings substitution, which gives rise to a series of compounds namely, flavonols, flavanones, flavones, anthocyanidins, flavanonols, chalcones, isoflavones, and flavanols. They are abundantly found in vegetables and fruits and exhibit antioxidant, free-radical scavenging activity, anti-cancer, cardioprotective, anti-diabetic, anti-inflammatory, anti-allergic, and anti-microbial action. The advent of modern molecular techniques and computational methodologies has thrown light on the molecular mechanism of action of these flavonoids, which was otherwise obscure. Hence this chapter aims to review the types, sources, chemistry, and molecular mechanisms of action of the various phytomolecules of flavonoid groups. 

Diabetes mellitus, is a chronic condition with dysregulated glucose levels and has been affecting a larger global population. The disease, if not controlled, can lead to several microvascular and macrovascular complications that will impede the patients' physical and mental well-being in addition to its economic burden. Many diabetic patients are unaware of the complications and hesitate to take medicines in the early phase of the disease condition. Furthermore, many patients have limited access to conventional antidiabetic drugs, which drives the search for newer agents or relying on alternative/complementary medicines. Ancient systems such as Ayurveda, traditional African and Chinese medicine, Japanese Kampo medicine, and other systems of medicine have identified many herbal/plants, and mineral-based agents for treating diabetes. Many such plants probably more than 800 and their extracts have been scientifically proven or tested using various experimental models of diabetes in animals. Despite several In vitro and In vivo studies reporting the effects of extracts of plants on blood glucose, only a few trials have been performed to validate their efficacy in treating humans with diabetes. An apparent mismatch in outcomes was observed while translating the effectiveness of these plants from an experimental animal study to a human study. These inconsistencies among animal and human studies were remarkable in some cases. There are several aspects responsible for these variations, such as variation in plant parts/extracts, dose, duration in different studies, the difference between animal models and human disease, and initiation of drug treatment in animal model, which is generally before the induction of diabetes or immediately after the induction of diabetes. This chapter focuses on the animal studies and human clinical trials conducted on plant-based extracts and other natural products and the outcomes in controlling or managing diabetes mellitus.

Viral infections are increasing continuously, and we do not have proper treatment. Currently, the COVID-19 pandemic is an emerging threat globally. If we look into the Indian perspective against COVID-19, plant-based medicine available in ancient literature has been used, like Charaka Samhita and current ayurvedic pharmacopeia. Many viral diseases will come in the future, for which, there is a need to establish concept-based treatment with scientifically-proven pharmacological action. The plant's primary and secondary metabolites are responsible for pharmacological activities. Many plants have shown their efficacy in viral infections through their phytochemicals. In this chapter, we have conceptualized the same and identified the plants with their metabolites, which can be a direction for future research on viral disease. Currently available allopathic treatments have efficacy but toxicities too.

For a better understanding of the diseases, the pathophysiology of the same is one of the components, as it gives a complete idea about how the viruses affect us. In the Indian traditional drug system, many folk medicines are available that need to establish the correlation with the targeted sites for a disease, which can give us the direction for future viral infections. The urgency is also to standardize these drugs for proper use among the global population. For identification, isolation of primary and secondary metabolites can help in treatment and drug targeting. The beauty of traditional medicine is that it is affordable because of its availability in different regions across the globe.

Herbs have been used as medicines since the beginning of time and are a rich source of many curative substances. In recent years, there has been a paradigm shift towards medicinal plant research due to the costlier modern drugs available in the market, and potential side effects and resistance developed by many conventional therapeutic agents. Pharmacological screening of medicinal plants using various scientific methods like in vitro, in vivo as well as in silico methods involving different experimental models provides emerging preclinical research exploring their mechanism of action. India is a large repository of many species of medicinal plants. According to a recent WHO estimate, a large amount of plant species, almost 21,000, have the capacity to be used as medicines. Medicinal plants such as Aloe barbadensis Mill., Ocimum tenuiflorum L., Curcuma longa L., Azadirachta indica A. Juss, Piper nigrum L., Cinnamomum verum J. Presl., Trifolium pratense L., Zingiber officinale Rosc, Carthamus tinctorius L., Piper nigrum, Allium sativum L and Andrographis paniculata (Burm.f.) Nees., Withania somnifera L. (Dunal), Cissus quadrangularis L., Plumbago zeylanica L., etc. reported to have therapeutic effects against severe common health ailments. Phytoconstituents present in medicinal herbs like alkaloids, tannins, saponins, ferric chloride, phenolics, emodins, and volatile oils showed potential therapeutic activity by interacting with the main targets in cells, such as receptor proteins, biomembranes, or nucleic acid. Biochemical outcomes of experimental studies showed that medicinal plants exert many pharmacological activities. The current review concentrates on the pharmacological activity of some important medicinal plants in various experimental animal models.

Traditional medicine has made extensive use of natural products, due to their extensive therapeutic applications. There is an increasing demand and acceptance of the use of medicinal plants due to their efficacy. For about 60,000 years ago, plants have been used as drugs according to several works of literature. It is evident that the Citrus genus, belonging to the Rutaceae family, possesses a range of pharmacological activities, including anticancer, antidiabetic, antihyperlipidemic, antimicrobial, hepatoprotective activity, and cardiovascular activity. Polysaccharides present in pomelo (C. maxima) peels act on S180 (murine sarcoma cells) Tumour-Bearing Mice by improving splenic lymphocyte proliferation ability and inhibiting the activity of NK cells, and leaf extract act on prostate carcinoma DU145 Cells by suppressing constitutive STAT-3 activation. At the same time, alcoholic extract of Citrus aurantium bloom showed an appreciable effect against breast cancer and human colon adenocarcinoma cells with IC50 152.34 ± 0.75 μg/mL, 49.74 ± 0.75 μg/mL, and 96.23 ± 0.75 μg/mL respectively. The emulsion prepared from the volatile oil of C. sinensis reduced viability in colon cancer cell lines and simultaneously upregulated BAX/BCL2 along with the suppression of vascular endothelial growth factor. Bergamottin and 5- geranyloxy-7-methoxycoumarin obtained from Citrus bergamia downregulated the proliferation of neuroblastoma (SH-SY5Y) cells, inducing apoptosis and positively regulated cell population in the sub-G0/G1 phase. The elevated BAX, downregulated BCL-2, released cytochrome C (cyt. c) in the cytoplasm, and cleaved PARP in breast cancer cells suggest that phytochemical constituents in lemon seed extracts might be a useful source of antioxidants and induce cell death via the mitochondrial apoptosis pathway. Bergamottin, a furanocoumarin obtained from peels of Citrus hystrix fruits, showed promising activity against pancreatic carcinoma cells by inhibiting survival proteins in the AKT/mTOR pathway. The detailed information on different species of the Citrus genus in the field of antineoplastic pharmacology might add value to the scientific evaluation for exploring more medicinal applications of these plants.

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Prion-related diseases are age-related progressive disorders. Among neurodegenerative diseases, Parkinson’s disease is the second most common disease after Alzheimer’s. Every year, millions of people were affected by Parkinson’s disease. The formation of α-synuclein protein aggregation associated with degeneration of dopaminergic neurons is the main pathological hallmark of PD. Patients suffering from this disease live in an impairing condition and impose huge financial as well as psychological burdens on society. However, there is no definite treatment till now that can be used to treat Parkinson’s disease patients. The current treatment approaches only provide symptomatic relief but can not reverse the disease condition. Hence, there is a need to identify novel, definitive and minimal toxicity-exhibiting treatments for PD. Natural products, specifically medicinal plants, due to their never-matched chemical diversity, always act as a better source for drug discovery. Here, in this chapter, we have selected andrographolide, a plant-derived secondary metabolite of labdane triterpenoid extracted from Andrographis paniculate, a traditional herb. Andrographolide shows its neuroprotective potential in PD via exhibiting multiple mechanisms like decreasing neuroinflammation induced by microglial activation. Activating HSF1 and NRF2-mediated autophagy mechanisms in clearing α-synuclein protein aggregation and regenerating the degenerated dopaminergic neurons, ameliorate the PD symptoms. In this possible way, andrographolide provides a better chance to develop a novel therapeutic tool for treating Parkinson’s disease in the near future.

People of all ages are affected by the chronic complications of diabetes mellitus. Numerous synthetic medications have been developed to treat diabetes, which has become more common across the globe. These medications, while effective as antihyperglycemic medicines, come with a number of side effects. They are expensive and out of reach for the vast majority of people who live in underdeveloped nations. Due to their accessibility and harmless nature, medicinal plants have already been traditionally utilized to cure a variety of illnesses throughout history. Phytochemicals found in medicinal plants provide a number of health advantages. Healthcare professionals are looking into plant-based medicines as a potential supply of antidiabetic pharmaceuticals because of their high efficacy and lack of adverse effects as diabetes prevalence rises. The active phytoconstituents are being identified and thoroughly studied in order to gain a better understanding of the mechanism of action of therapeutic plants. Here, we focus on the perspectives of pharmacologically active phytomolecule formulations produced from medicinal plants that demonstrate antidiabetic action and the role they now play in managing and treating diabetes in the present scenario. These natural molecules might be suitable for developing new approaches to treatment or potent treatment options for diabetes.