The Potential of Epigallocatechin Gallate in Targeting Cancer Stem Cells: A Comprehensive Review.

The dreadful scenario of cancer prevails due to the presence of cancer stem cells (CSCs), which contribute to tumor growth, metastasis, invasion, resistance to chemo- and radiotherapy, and recurrence. CSCs are a small subpopulation of cells within the tumor that are characterized by self-renewal capability and have the potential to manifest heterogeneous lineages of cancer cells that constitute the tumor. The major bioactive green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been fruitful in downgrading cancer stemness signaling and CSC biomarkers in cancer progression. EGCG has been evidenced to maneuver extrinsic and intrinsic apoptotic pathways in order to decrease the viability of CSCs. Cancer stemness is intricately related to epithelial-mesenchymal transition (EMT), metastasis and therapy resistance, and EGCG has been evidenced to regress all these CSC-related effects. By inhibiting CSC characteristics EGCG has also been evidenced to sensitize the tumor cells to radiotherapy and chemotherapy. However, the use of EGCG in in vitro and in vivo cancer models raises concern about its bioavailability, stability and efficacy against spheroids raised from parental cells. Therefore, novel nano formulations of EGCG and adjuvant therapy of EGCG with other phytochemicals or drugs or small molecules may have a better prospect in targeting CSCs. However, extensive clinical research is still awaited to elucidate a full proof impact of EGCG in cancer therapy.

Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies.

Rosmarinic acid (RA) is a natural phenolic compound present in culinary herbs of the Boraginaceae, Lamiaceae/Labiatae, and Nepetoideae families. While the medicinal applications of these plants have been known for ages, RA has only been relatively recently established as an effective ameliorative agent against various disorders including cardiac diseases, cancer, and neuropathologies. In particular, several studies have confirmed the neuroprotective potential of RA in multiple cellular and animal models, as well as in clinical studies. The neuroprotective effects mediated by RA stem from its multimodal actions on a plethora of cellular and molecular pathways; including oxidative, bioenergetic, neuroinflammatory, and synaptic signaling. In recent years, RA has garnered tremendous interest as an ideal therapeutic candidate for treating neurodegenerative diseases. This review first briefly discusses the pharmacokinetics of RA and then proceeds to detail the neuroprotective mechanisms of RA at the molecular levels. Finally, the authors focus on the ameliorative potential of RA against several central nervous system (CNS) disorders, ranging from neuropsychological stress and epilepsy to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Lewy body dementia, and amyotrophic lateral sclerosis.

Complexity of Tumor Microenvironment: Therapeutic Role of Curcumin and Its Metabolites.

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions.

The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.

Traditional uses, phytochemistry and pharmacological attributes of Pterocarpus santalinus and future directions: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterocarpus santalinus, an ancient folk medicine, is endemic to the eastern ghats of south India, and the heartwood is prescribed since time immemorial for the mitigation of inflammatory disorders in traditional practice and ayurvedic system of medicines. AIM OF THE STUDY: This review aims to provide collective pieces of information of the traditional uses, phytochemicals, and pharmacological facets of P. santalinus, with an intuition for promoting future research to explore its pharmaceutical potential as a therapeutic agent against modern maladies. MATERIAL AND METHODS: Extensive literature search was performed to collate the data by using various electronic search engines. A network pharmacology-based approach is incorporated for validation of traditional claims orbiting around anti-inflammatory properties and directed its future exploration against obesity, ovarian inflammation, ovarian folliculogenesis, and inflammatory breast cancer. RESULTS: In a nutshell, the present review encompasses the phytochemistry, pharmacology of this species intending to sensitize the scientific community for future research on this promising plant. Nearly 85 chemical constituents are reported from the plants wherein bark and leaves are enriched with the lupane and oleanane class of triterpene while sesquiterpenes and polyphenolic compounds are predominantly present in the heartwood of the plant. Although phytochemical investigations are being reported since the mid-twentieth century however there has been recent interest in the evaluation of biological activities such as anti-inflammatory, anti-oxidant, anti-cancer, anti-viral, etc. CONCLUSION: In conclusion, a systematic phytochemical analysis and pharmacological exploration in close collaboration for establishing the therapeutic potential of the chemical constituents present in P. santalinus is recommended to substantiate the traditional claims for bringing it into the mainstream pharmaceutical and commercial utilization.

Effect of gamma irradiation on metallothionein protein expression in Plantago ovata Forsk.

PURPOSE: The effect of gamma rays on metallothionein (MT) expression was studied using the medicinal plant Plantago ovata as the test system. MATERIALS AND METHODS: Western blotting and Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used for this purpose. RESULTS: Western blot analysis showed significant induction of metallothionein protein following gamma exposure and that induction was highest at 20 Gy gamma dose. At higher gamma doses (100 Gy) MT expression level declined due to degeneration of cells. MALDI-TOF MS analysis indicated the presence of low molecular weight (7-8 kD) MT molecules following the lower radiation doses. CONCLUSION: It was concluded from the MALDI-TOF MS result that low gamma exposure leads to expression of MT-like protein. At high doses of gamma ray, MT homologues or MT-like protein were not identified, possibly because they might have precipitated due to uncontrolled cross-linking and non-specific aggregation.

Formulation of nutrient medium for in vitro somatic embryo induction in Plantago ovata forsk.

A nutrient medium has been formulated by altering the macro- and micro-elemental concentration in the culture medium for in vitro somatic embryo induction of economically important medicinal plant Plantago ovata Forsk .A comparison was made between induced embryos with normal embryos (produced in Murashige and Skoog (MS) medium) to observe frequency of embryo induction and also to determine regeneration efficiency. In the present investigation, three different media have been formulated. Among them, FM3 (formulated media, treatment 3) was the most suitable for increasing the frequency of somatic embryo production and regeneration of P. ovata Forsk. Better result was obtained using formulated medium than with MS medium.

PIXE analysis of trace elements in relation to chlorophyll concentration in Plantago ovata Forsk.

Plantago ovata Forsk - an economically important medicinal plant - was analyzed for trace elements and chlorophyll in a study of the effects of gamma radiation on physiological responses of the seedlings. Proton-induced X-ray emission (PIXE) technique was used to quantify trace elements in unirradiated and gamma-irradiated plants at the seedling stage. The experiments revealed radiation-induced changes in the trace element and chlorophyll concentrations.

Analysis of trace elements during different developmental stages of somatic embryogenesis in Plantago ovata Forssk using energy dispersive X-ray fluorescence.

Energy dispersive X-ray fluorescence (ED-XRF) technique has been used for the determination of trace element profile during different developmental stages of somatic embryogenic callus of an economically important medicinal plant, Plantago ovata Forssk. Somatic embryogenesis is a plant tissue culture-based technique, which is used for plant regeneration and crop improvement. In the present investigation, elemental content was analysed using ED-XRF technique during different developmental stages and also determine the effect of additives--casein hydrolysate and coconut water on the trace elemental profile of embryogenic callus tissue of P. ovata. Subsequent experiments showed significant alteration in the concentration of K, Ca, Mn, Fe, Zn, Cu, Br, and Sr in both the embryogenic and non-embryogenic callus. Higher K, Ca, Fe, Cu, and Zn accumulation was in embryogenic tissue stage compared to other stages, suggesting these elements are crucial for successful embryogenesis. The results suggest that this information could be useful for formulating a media for in vitro embryo induction of P. ovata.