Persistent hair loss is a major cause of psychological distress and compromised quality of life in millions of people worldwide. Remarkable progress has been made in understanding the molecular basis of hair loss and identifying valid intracellular targets for designing effective therapies for hair loss treatment. Whereas a variety of growth factors and signaling pathways have been implicated in hair cycling process, the activation of Wnt/β-catenin signaling plays a central role in hair follicle regeneration. Several plant-derived chemicals have been reported to promote hair growth by activating Wnt/β-catenin signaling in various in vitro and in vivo studies. This mini-review sheds light on the role of Wnt/β-catenin in promoting hair growth and the current progress in designing hair loss therapies by targeting this signaling pathway.

Extracellular and intracellular oxidants or electrophiles are key contributors to the damages in cellular macromolecules, such as DNA, proteins and lipids. Nrf2 is a master transcription factor that modulates a cellular antioxidant response program and plays an important role in the protection against oxidants and electrophiles. Keap1 is a regulator of Nrf2 by serving as a substrate adaptor for Cullin3-dependent E3 ubiquitin ligase. While Nrf2 activation is a feasible strategy for treatment of age-related diseases, aberrant Nrf2 activation also confers a selective growth advantage of tumor cells during chemotherapy or radiotherapy. In the present review, we provide an overview of the Keap1-Nrf2-ARE system, the domain organization of Nrf2 and Keap1, and the regulatory mechanisms of Nrf2 proteolysis by Keap1. We also discuss how Nrf2 prevents tumor promotion, hampers the sensitivity of selected tumors against chemotherapy or radiotherapy, and reprograms the metabolism to facilitate the tumor proliferation. Finally, we illustrate the current status in the development of Nrf2 chemical activators and inhibitors for the use of potential chemopreventive agents and chemotherapeutic adjuvants, respectively.

Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A.

Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, anti-inflammatory, antiallergic, bone remodeling, neuroprotective, hair growth promoting, anticancer, and antidiabetic properties. Many of these bioactivities are supported by mechanistic details, such as the modulation of various intracellular signaling pathways involved in precipitating tissue inflammation, tumor growth and progression, bone loss, and neurodegeneration. The key molecular targets of costunolide include, but are not limited to, intracellular kinases, such as mitogen-activated protein kinases, Akt kinase, telomerase, cyclins and cyclin-dependent kinases, and redox-regulated transcription factors, such as nuclear factor-kappaB, signal transducer and activator of transcription, activator protein-1. The compound also diminished the production and/expression of proinflammatory mediators, such as cyclooxygenase-2, inducible nitric oxide synthase, nitric oxide, prostaglandins, and cytokines. This review provides an overview of the therapeutic potential of costunolide in the management of various diseases and their underlying mechanisms.

The functional aspect of scalp hair is not only to protect from solar radiation and heat/cold exposure but also to contribute to one’s appearance and personality. Progressive hair loss has a cosmetic and social impact. Hair undergoes three stages of hair cycle: the anagen, catagen, and telogen phases. Through cyclical loss and new-hair growth, the number of hairs remains relatively constant. A variety of factors, such as hormones, nutritional status, and exposure to radiations, environmental toxicants, and medications, may affect hair growth. Androgens are the most important of these factors that cause androgenic alopecia. Other forms of hair loss include immunogenic hair loss, that is, alopecia areata. Although a number of therapies, such as finasteride and minoxidil, are approved medications, and a few others (e.g., tofacitinib) are in progress, a wide variety of structurally diverse classes of phytochemicals, including those present in ginseng, have demonstrated hair growth-promoting effects in a large number of preclinical studies. The purpose of this review is to focus on the potential of ginseng and its metabolites on the prevention of hair loss and its underlying mechanisms.

Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2′,4′,6′-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a wide array of preclinical studies. The efficacy of phloretin in suppressing xenograft tumor growth in athymic nude mice implanted with a variety of human cancer cells, and the ability of the compound to interfere with cancer cells signaling, have made it a promising candidate for anti-cancer drug development. Mechanistically, phloretin has been reported to arrest the growth of tumor cells by blocking cyclins and cyclin-dependent kinases and induce apoptosis by activating mitochondria-mediated cell death. The blockade of the glycolytic pathway via downregulation of GLUT2 mRNA and proteins, and the inhibition of tumor cells migration, also corroborates the anti-cancer effects of phloretin. This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent.