Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, coumarins have attracted intense research interest. Of great interest is the possibility that this class of molecules could be a source of drugs for the therapy of several diseases. These include recent insights into inhibiting cell proliferation by interfering with mitotic spindle microtubule function, decrease Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M phases to interfere with processes of cell division, suppress O2(-) generation in leukocytes, inhibit different protein kinases, modulate the signalings, induce carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a mechanism inhibiting inflammation, progress in structure modification to increase in anti-fungal action, to broaden against bacteria spectrum, to enhance inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic side effects than the indanedione derivatives, they can be applied as an oral anticoagulant commonly for preventing venous thromboembolism following orthopedic surgery, recurrent myocardial infarction and the treatment of systemic embolism in atrial fibrillation, together with the significant advances in the basis of drug action. It is therefore useful to build up some correlations with the data available in order to better explore the molecular and cellular mechanism of coumarin action in the treatment of diseases. This review will focus on recent advances in molecular and cellular mechanisms of coumarin action involved with the relationship between structure and activity.

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3β may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3β has been implicated in mediation of mitochondrial functions. GSK-3β exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3β might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Intensive efforts have been made for exploring GSK-3β inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3β. The key roles of GSK-3β in mediation of mitochondrial functions are discussed in this review.

Colorectal cancer (CRC) is one of the major health threats in developed countries. Changes in dietary components, such as more protein and lipid intake, can increase the risk of CRC. Diet affects CRC in many ways. They regulate the composition and function of gut microbiota, which have an amazing metabolic capacity and can produce short chain fatty acids (SCFAs), such as propionate, acetate, and butyrate. Butyrate is a principal energy source for colonic epithelial cells and plays an important role in maintaining the stability of gut microbiota and the integrity of intestinal epithelium. However, there are few studies reviewing the anti-CRC potentials of butyrate. This review summarizes the recent research progresses in the effect of gut microbiota imbalance and the decrease in intestinal microbial metabolite butyrate caused by unbalanced diet on CRC development, and discusses the mechanisms of butyrate-induced anti-CRC activities, which may guide people to prevent CRC by improving diet structures.

Nobiletin (NOB) chemically known as 5,6,7,8,3′,4′-hexamethoxyflavone is a dietary polymethoxylated flavonoid found in Citrus fruits. Recent evidences show that NOB is a multifunctional pharmaceutical agent. The various pharmacological activities of NOB include neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. These events may be underpinned by modulation of signaling cascades, including PKA/ERK/MEK/CREB, NF-κB, MAPK, Ca2+/CaMKII, PI3K/Akt1/2, HIF-1α, and TGFβ signaling pathways. The metabolites may exhibit stronger beneficial effects than NOB on diseases pathogenesis. The biological activities of NOB have been clarified on many systems. This review aims to discuss the pharmacological effects of NOB with specific mechanisms of actions. NOB may become a promising candidate for potential drug development. However, further investigations of NOB on specific intracellular targets and clinical trials are still needed, especially for in vivo medical applications.

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Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated from Magnolia officinalis, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-κB/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.

Osteoarthritis (OA) constitutes a major health problem. Different signaling pathways are involved that impair homeostasis, but the cross-talk between them (although well investigated and partly understood), remains unclear. HIF-1α promotes chondrocyte differentiation and survival, while HIF-2α coactivates with β-catenin and NF-κB pathways to promote chondrocyte apoptosis and endochondral ossification. Depending on the ALK1/ALK5 ratio in chondrocytes, the TGFβ pathway can play an anabolic or catabolic role. TGFβ1 can activate the β-catenin signaling pathway via ALK5, Smad3, PI3K, and PKA pathways. The mediator Axins balance TGF-β and Wnt/β-catenin signaling during chondrocyte proliferation and maturation. However, the biological functions of Wnt/β-catenin signaling are still controversial. Both excessive and insufficient β-catenin levels may impair the homeostasis of articular chondrocytes by enhancing pathological maturation and apoptosis, respectively; loss- and gain-of-functions of β-catenin cause apoptosis at the center of the joint and chondrocyte maturation at the periphery, depending on the vascularity. The NF-κB transcription factor can be triggered by a host of stress-related stimuli including pro-inflammatory cytokines. The recent discovery of functional cross-regulation between these pathways has shown complex roles for HIF-1α/HIF-2α, TGFβ/BMP, Wnt/β-catenin, and NF-κB signaling pathways in the pathogenesis of OA. This has important implications for potential therapeutic agents directed at these pathways. This review attempts to cover the literature of the past three years dealing with the biology and pathology of the HIF-1α/-2α, TGFβ/BMP, Wnt/β-catenin, and NF-κB/cytokines signaling pathways in OA.

Dihydromyricetin is a flavonoid isolated from Ampelopsis grossedentata, which is traditionally used in China. Dihydromyricetin exhibits health-benefiting activities with minimum adverse effects. Dihydromyricetin has been demonstrated to show antioxidative, anti-inflammatory, anticancer, antimicrobial, cell death-mediating, and lipid and glucose metabolism-regulatory activities. Dihydromyricetin may scavenge ROS to protect against oxidative stress or potentiate ROS generation to counteract cancer cells selectively without any effects on normal cells. However, the low bioavailability of dihydromyricetin limits its potential applications. Recent research has gained positive and promising data. This review will discuss the versatile effects and clinical prospective of dihydromyricetin.