Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.

Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use.Communicated by Ramaswamy H. Sarma.

Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells.

Fucoxanthin is a carotenoid produced by brown algae and diatoms. This compound has several biological properties such as antioxidant, anti-obesity, anti-diabetic, anticancer, and antimicrobial activities. Unfortunately, until now the latter effect has been poorly confirmed. The aim of this study was an evaluation of fucoxanthin activity against 20 bacterial species. Antimicrobial effect of fucoxanthin was determined by using the agar disc-diffusion and micro-dilution methods. The studied carotenoid acted against 13 bacteria growing in aerobic conditions. It was observed to have a significantly stronger impact on Gram-positive than Gram-negative bacteria. Mean zones of growth inhibition (ZOIs) for Gram-positive bacteria ranged between 9.0 and 12.2 mm, while for Gram-negative were from 7.2 to 10.2 mm. According to the agar disc-diffusion method, the highest activity of fucoxanthin was exhibited against Streptococcus agalactiae (mean ZOI 12.2 mm), Staphylococcus epidermidis (mean ZOI 11.2 mm), and Staphylococcus aureus (mean ZOI 11.0 mm), and in the microdilution test towards Streptococcus agalactiae with the minimal inhibitory concentration (MIC) of 62.5 µg/mL. On the other hand, fucoxanthin was not active against strict anaerobic bacteria.

Fucoxanthin—An Antibacterial Carotenoid

Intermediate filaments (IFs), in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, playing a vital role in mechanotransduction and in providing mechanical stability to cells (Figure 1) [1]. Despite the importance of IF mechanics for cell biology and cell mechanics, the structural basis for their mechanical properties remains unknown. Specifically, our understanding of fundamental filament properties, such as the basis for their great extensibility, stiffening properties, and their exceptional mechanical resilience remains limited. This has prevented us from answering fundamental structure-function relationship questions related to the biomechanical role of intermediate filaments, which is crucial to link structure and function in the protein material’s biological context.Copyright © 2010 by ASME

Hierarchical Structure Controls Nanomechanical Properties of Vimentin Intermediate Filaments

The roles of ZEB1 in tumorigenic progression and epigenetic modifications.

We had previously reported anticancer activity in the water extract (WEX) of Ashwagandha leaves, and identified Triethylene glycol (TEG) as an active tumor suppressor component. In this study, we investigated anti-migratory and anti-angiogenesis activities of WEX and TEG. We conducted in vitro and in vivo experiments using TEG, and its two derivatives, Triethyleneglycol dimethacrylate (TD-10), and Tetraethyleneglycol dimethacrylate (TD-11). The data revealed strong anticancer and anti-metastasis potentials in the derivatives. Non-toxic, anti-migratory doses of the derivatives showed inhibition of canonical Wnt/β-catenin axis and consequent downregulation of EMT-signaling proteins (Vimentin, MMPs and VEGF). These results endorse that the TD-10 and TD-11 have potential to safely put a check on the aggressiveness of the metastatic cells and therefore represent promising candidates for the treatment of metastatic cancers.

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Identification and Functional Characterization of Anti-metastasis and Anti-angiogenic Activities of Triethylene Glycol Derivatives.

Experimental evidence and mechanism of action of some popular neuro-nutraceutical herbs.

Hydroponics, growing plants in water with appropriate nutrients and other cultivation conditions including temperature and CO2, is a convenient way to (i) avoid the unpredictable extreme weather conditions that affect the cultivation of plants in soil, (ii) safe guard against environmental stresses including industrial pollutants and pesticides and (iii) ensure stable content of active components that are important for value of plants as either functional food or medicine. Considerable advances have been made in establishment of hydroponics cultivation conditions for a variety of leafy vegetables. However, their use has not expanded to medicinal herbs. In this chapter, we review the very first hydroponic cultivation of Ashwagandha, a medicinal herb.

Establishment of Hydroponic Cultivation of Ashwagandha for Active Ingredient Enriched Leaves

Ageing is an innate indispensable physiological process largely conceived as general decline in body functions and defense mechanisms. While ageing per se is not a disease, there are many age-related pathologies, modulation of which is considered as anti-ageing in several ways. Chronic stress often triggers senescence-inducing mechanisms manifested as premature/rapid ageing. The latter is associated with a high incidence of stress-related disorders such as cancer, neurodegeneration, metabolic disorders and muscle/bone dysfunctions. Cell culture system provides an easy and convenient experimental system to study mechanisms of natural (replicative) and stress-induced ageing. We, over the years, have researched molecular mechanisms of ageing and age-related pathologies, and their modulation with natural compounds using cell culture as a model system. Among several others, bioactives from Ashwagandha (Withania somnifera) have emerged as useful natural compounds with a variety of activities and are hence predicted to assist in health care in stress and disease states. In this chapter, we describe highlights of our research work demonstrating the therapeutic potential of Ashwagandha leaves that offer advantage over roots in terms of availability, processing and being enriched with active compounds.

Why Ashwagandha for Healthy Ageing? Evidence from Cultured Human Cells

Stress is a state that triggers change in normal physiology and recognized by human body and brain as an unfavorable event causing concern, worry or anxiety. It may vary from physical, metabolic, physiological or emotional often culminating into wide range of ailments that may range from common cold, decline in functional efficacy of body systems or even cancer. Skin is the largest tissue of the body and makes the first interface with the environment. Skin color and characteristics are highly influenced by environment stress. A variety of natural compounds have been used for anti-stress and disease preventive potentials in worldwide traditional home medicine systems. They have recently attracted attention in research laboratories to dissect their mode of action to promote safe and economic drug development. We have earlier identified anti-stress and anti-aging activities in Withania somnifera, Helicteres angustifolia and honeybee propolis using human cultured normal and cancer cells. In the present study, we explored the effect of tamarind seed extracts prepared in water or 95% ethanol. In cell-based assays, we found that the extracts were safe to use in viable cells (in the range of 0.01-1.0%, for at least 4 weeks). Consistently, molecular studies revealed no effect on the expression/activity of cancer promoting proteins. We recruited oxidative stress models, such as, hydrogen peroxide (H2O2), ultraviolet radiation (UV) and diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (OAG). Investigation on anti-stress potential of the extracts revealed that they do not offer remarkable protection against stress caused by either H2O2 or UV, however, significantly compromised OAG-induced melanogenesis. The preliminary data warrant further investigations on the active components and mechanism of action to develop useful natural compounds/extracts for manipulation of melanogenesis that plays important role in response of cells to UV and its consequences including DNA damage, oxidative stress and related diseases.

Sukant Garg

Papers

Identification and Functional Characterization of Anti-metastasis and Anti-angiogenic Activities of Triethylene Glycol Derivatives.

Experimental evidence and mechanism of action of some popular neuro-nutraceutical herbs.

Establishment of Hydroponic Cultivation of Ashwagandha for Active Ingredient Enriched Leaves

Why Ashwagandha for Healthy Ageing? Evidence from Cultured Human Cells

Bioactivities in the tamarind seed extracts: A preliminary study