Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.

Therapeutic potential of resveratrol: the in vivo evidence.

Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects – A review

Dietary phenolics: chemistry, bioavailability and effects on health.

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

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Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update

Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol has been shown to suppress the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for the suppression of angiogenesis by this stilbene. Resveratrol also has been shown to potentiate the apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation. Phamacokinetic studies revealed that the target organs of resveratrol are liver and kidney, where it is concentrated after absorption and is mainly converted to a sulfated form and a glucuronide conjugate. In vivo, resveratrol blocks the multistep process of carcinogenesis at various stages: it blocks carcinogen activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity, and suppresses tumor initiation, promotion and progression. Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer.

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Role of Resveratrol in Prevention and Therapy of Cancer: Preclinical and Clinical Studies

Various plant metabolites are useful for human life, and the induction and reduction of these metabolites using modern biotechnical technique is of enormous potential important especially in the fields of agriculture and health. Plant Metabolism and Biotechnology describes the biosynthetic pathways of plant metabolites, their function in plants, and some applications for biotechnology. Topics covered include: Photosynthetic carbon metabolism Starch and sugar biosynthesis Cellulose (cell wall) biosynthesis Lipid biosynthesis Nitrogen fixation and assimilation Sulfur metabolism Amino acid metabolism Nucleotide metabolism Purine alkaloids Nicotine Benzylisoquinoline alkaloids (morphine, codeine) Flavonoid metabolism Pigment metabolism Use of the metabolome for biotechnology Application to biomass improvement and biodiesel Plant Metabolism and Biotechnology is an essential guide to this important field for researchers and students of biochemistry, plant biology, metabolic engineering, biotechnology, food science, agriculture, and medicine.

Plant metabolism and biotechnology

Biosynthesis of Purine Alkaloids in Camellia Plants

The aim of the present study was to investigate the metabolic fate of guanine nucleotides in higher plants The rate of uptake of [8- 14 C]guanosine by suspension-cultured Catharanthus roseus cells was more than 20 times higher than that of [8- 14 C]guanine The rate of uptake of [8- 14 C]guanosine increased with the age of the culture Pulse-chase experiments with [8- 14 C]guanosine revealed that some of the guanosine that had been taken up by the cells was converted to guanine nucleotides and incorporated into nucleic acids A significant amount of [8- 14 C]guanosine was degraded directly to xanthine, allantoin and allantoic acid, with the generation of l4 CO 2 as the final product The rate of salvage of [8- 14 C]guanosine for the synthesis of nucleic acids was highest in young cells, while the rate of degradation increased with the age of the cells In segments of roots from Vigna mungo seedlings, nearly 50% of the [8- 14 C]guanosine that had been absorbed over the course of 15 min was recovered in guanine nucleotides A significant amount of the radioactivity in nucleotides became associated with nucleic acids and ureides during 'chase' periods In segments of young leaves of Camellia sinensis, [8- 14 C]guanosine was initially incorporated into guanine nucleotides, nucleic acids, theobromine and ureides, and the radioactivity in these compounds was transferred to caffeine and CO 2 during a 24-h incubation Our results suggest that guanosine is an intermediate in the catabolism of guanine nucleotides and that it is re-utilised for nucleotide synthesis by 'salvage' reactions Guanosine was catabolised by the conventional degradation pathway via xanthine and allantoin In some plants, guanosine is also utilised for the formation of ureide or the biosynthesis of caffeine

Metabolic fate of guanosine in higher plants

Comparison of the formation of nicotinic acid conjugates in leaves of different plant species.

Abstract The metabolism of [8-14C ]adenine and [2-14C]caffeine was examined in leaf segments from flush shoots of tea cultivars with high and low caffeine content. The caffeine biosynthesis pathway from AMP via theobromine was operative in both high and low caffeine containing cultivars. There was a m ore rapid rate of caffeine biosynthesis from [8-14C ]adenine in the high caffeine cultivars while the rate of degradation of both adenine nucleotides and caffeine into CO2 was greatest in cultivars with a low endogenous caffeine content. Cell-free p reparations from tea shoots contained an N-methyltransferase, that is a keyenzyme in the caffeine biosynthesis pathway; more in-vitro activity was detected in preparations from high caffeine containing cultivars. The data obtained suggest that the high caffeine containing cultivars have a more rapid rate of caffeine biosynthesis and a slower rate of caffeine catabolism than cultivars with a low endogenous caffeine content

Hiroshi Ashihara

Papers

Plant metabolism and biotechnology

Biosynthesis of Purine Alkaloids in Camellia Plants

Metabolic fate of guanosine in higher plants

Comparison of the formation of nicotinic acid conjugates in leaves of different plant species.

Caffeine metabolism in high and low caffeine containing cultivars of camellia sinensis