Research progress of proanthocyanidins and anthocyanidins.

Proanthocyanidins (PA) are polyphenol compounds that are widely distributed in the bark, fruit core, skin, or seeds of various plants. Anthocyanidins are water-soluble natural pigments widely found in plants. They are all flavonoids, a major coloring substance in plants and fruits. In recent years, research into PA and anthocyanins has become increasingly popular because of their excellent anti-oxidation, scavenging of reactive oxygen free radicals and other physical and chemical activities, and their anti-cancer, vision protection, aging prevention, skin beauty pharmacological, and nutraceutical effects. Especially, recent systematic reviews and meta-analyses indicate their value, safety, and efficacy in the prevention, adjuvant therapy, and management of cardiometabolic disease. Here, we summarize their research progress from the aspects of chemical structure, biosynthetic pathways, distribution, extraction and separation, coloration, efficacy, and potential. The comparison between them might provide a reference for their development and efficient utilization. However, more large-sample-size randomized controlled trials and high-quality studies are needed to firmly establish their clinical efficacy.

Proanthocyanidins: Components, Pharmacokinetics and Biomedical Properties.

Proanthocyanidins (PAs) are a group of polyphenols enriched in plant and human food. In recent decades, epidemiological studies have upheld the direct relationship between PA consumption and health benefits; therefore, studies on PAs have become a research hotspot. Although the oral bioavailability of PAs is quite low, pharmacokinetics data revealed that some small molecules and colonic microbial metabolites of PAs could be absorbed and exert their health beneficial effects. The pharmacological effects of PAs mainly include anti-oxidant, anticancer, anti-inflammation, antimicrobial, cardiovascular protection, neuroprotection, and metabolism-regulation behaviors. Moreover, current toxicological studies show that PAs have no observable toxicity to humans. This review summarizes the resources, extraction, structures, pharmacokinetics, pharmacology, and toxicology of PAs and discusses the limitations of current studies. Areas for further research are also proposed.

SNX17 (Sorting Nexin 17) Mediates Atrial Fibrillation Onset Through Endocytic Trafficking of the Kv1.5 (Potassium Voltage-Gated Channel Subfamily A Member 5) Channel.

BACKGROUND: Kv1.5 (Potassium voltage-gated channel subfamily A member 5) has been regarded as a promising target of interventions for atrial fibrillation (AF). SNX17 (sorting nexin 17), a member of the SNXs (sorting nexin family), regulates the intracellular trafficking of membrane proteins through its FERM (four-point-one, ezrin, radixin, moesin) domain. However, whether SNX17 regulates the trafficking process of Kv1.5 remains unknown. METHODS: A SNX17 knockout rat line was generated to test the role of SNX17 in atrial electrophysiology. The protein expression of SNX17 and membrane ion channels was detected by Western blotting. Electrophysiology changes in the atrial tissue and myocytes were analyzed by optical mapping and patch clamp, respectively. Acetylcholine and electrical stimulation were used to induce AF, and ECG recording was adopted to assess the influence of SNX17 deficiency on AF susceptibility. The spatial relationship between Kv1.5 and SNX17 was evaluated by immunostaining and confocal scanning, and the functional region of SNX17 regulating Kv1.5 trafficking was identified using plasmids with truncated SNX17 domains. RESULTS: Embryonic death occurred in homozygous SNX17 knockout rats. SNX17 heterozygous rats survived, and the level of the SNX17 protein in the atrium was decreased by ≈50%. SNX17 deficiency increased the membrane expression of Kv1.5 and atria-specific ultrarapid delayed rectifier outward potassium current ( IKur) density, resulting in a shortened action potential duration, and eventually contributing to AF susceptibility. Mechanistically, SNX17 facilitated the endocytic sorting of Kv1.5 from the plasma membrane to early endosomes via the FERM domain. CONCLUSIONS: SNX17 mediates susceptibility to AF by regulating endocytic sorting of the Kv1.5 channel through the FERM domain. SNX17 could be a potential target for the development of new drugs for AF.

Pinus massoniana Bark Extract: Structure-Activity Relationship and Biomedical Potentials.

Proanthocyanidins (PAs) belong to the condensed tannin subfamily of natural flavonoids. Recent studies have shown that the main bioactive compounds of Pinus massoniana bark extract (PMBE) are PAs, especially the proanthocyanidins B series, which play important roles in cell cycle arrest, apoptosis induction and migration inhibition of cancer cells in vivo and in vitro. PA-Bs are mixtures of oligomers and polymers composed of flavan-3-ol, and the relationship between their structure and corresponding biomedical potentials is summarized in this paper. The hydroxyl at certain positions or the linkage between different carbon atoms of different rings determines or affects their anti-oxidant and free radical scavenging bioactivities. The degree of polymerization and the water solubility of the reaction system also influence their biomedical potential. Taken together, PMBE has a promising future in clinical drug development as a candidate anticancer drug and as a food additive to prevent tumorigenesis. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of PMBE, its active constituents and their derivatives.

Pine bark extracts: nutraceutical, pharmacological, and toxicological evaluation.

Proanthocyanidins are among the most abundant constituents in pine bark extracts (PBEs). This review summarizes medical research on PBEs from Pinus pinaster, Pinus radiata, Pinus massoniana, and other less well characterized species. The precise mechanisms of the important physiologic functions of PBE components remain to be elucidated, but there is evidently great potential for the identification and development of novel antioxidant, anti-inflammatory, cardiovascular, neuroprotective, and anticancer medicines. Although toxicological data for PBEs are limited, no serious adverse effects have been reported. PBEs, therefore, may have potential as nutraceuticals and pharmaceuticals and should be safe for use as food ingredients.

Effects of Pinus massoniana bark extract on the adhesion and migration capabilities of HeLa cells.

Pinus massoniana Lamb is a Chinese red pine species used in traditional medicine for the treatment of a variety of human health disorders. Recent studies have shown that P. massoniana bark extract (PMBE) has an anti-proliferation effect on cancer cells. However, it is not clear if PMBE affects cancer cell migration and/or invasion. We tested the effect of PMBE, which has B-type procyanidin as its main constituent, on the adhesion and migration capabilities of HeLa cells, a human cervical cancer cell line, cultured in vitro. Our results showed that PMBE has no significant effect on the adhesion capability of HeLa cells, but strongly inhibits their migration. This finding suggests that PMBE could be a potential therapeutic agent for metastatic cancer.

Effects of Pinus massoniana bark extract on cell proliferation and apoptosis of human hepatoma BEL-7402 cells.

AIM: To study the effects of Pinus massoniana bark extract (PMBE) on cell proliferation and apoptosis of human hepatoma BEL-7402 cells and to elucidate its molecular mechanism. METHODS: BEL-7402 cells were incubated with various concentrations (20-200 microg/mL) of PMBE for different periods of time. After 48 h, cell proliferation was determined by 3-(4,5-dimethyl-thiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was evaluated by morphological observation, agarose gel electrophoresis, and flow cytometry analysis. Possible molecular mechanisms were primarily explored through immunohistochemical staining. RESULTS: PMBE (20-200 microg/mL) significantly suppressed BEL-7402 cell proliferation in a time- and dose-dependent manner. After treatment of BEL-7402 cells with 160 microg/mL PMBE for 24, 48, or 72 h, a typical apoptotic "DNA ladder" was observed using agarose gel electrophoresis. Nuclear condensation and boundary aggregation or split, apoptotic bodies were seen by fluorescence and electron microscopy. Sub-G1 curves were displayed by flow cytometry analysis. PMBE decreased the expression levels of Bcl-2 protein in a time-dependent manner after treatment of cells with 160 microg/mL PMBE. CONCLUSION: PMBE suppresses proliferation of BEL-7402 cells in a time- and dose-dependent manner and induces cell apoptosis by possibly downregulating the expression of the bcl-2 gene.

Potential biomedical properties of Pinus massoniana bark extract.

This study examined the potential biomedical properties of a bark extract from Pinus massoniana Lamb (PMBE). Its antioxidant activity, superoxide anion radical scavenging and free radical scavenging activities were examined. The antioxidant activity in a linoleic acid emulsion increased with increasing amounts of PMBE, with 100, 300 and 500 microg PMBE inhibiting 64.7%, 68.6% and 76.6% of peroxidation, respectively. Similarly, the radical scavenging activity by PMBE increased in a dose-dependent manner, suggesting that there may be a correlation between the antioxidant and scavenging activities. In addition, the effect of PMBE on human hepatocellular carcinoma BEL-7402 cells and normal liver L-02 cells was investigated in vitro. PMBE appeared to inhibit selectively the growth of BEL-7402 and slightly promoted the growth of L-02. Taken together, the results indicate that PMBE is a natural antioxidant that could potentially be used as a food supplement or as a candidate precursor substance for new anticancer therapeutics.