Shexiang Baoxin Pill treats acute myocardial infarction by promoting angiogenesis via GDF15-TRPV4 signaling.

Angiogenesis has been considered a pivotal strategy for treating ischemic heart disease. One possible approach, the Shexiang Baoxin Pill (MUSKARDIA), has been noted to promote angiogenesis, but its underlying mechanism is still largely unknown. We aimed to determine the effects of MUSKARDIA on acute myocardial infarction (AMI), as well as the underlying mechanistic bases. AMI was induced in rats, using left anterior descending coronary arterial occlusion, and either 6 (low) or 12 (high-dose) mg/kg/day of MUSKARDIA was administered for 56 days. We found that MUSKARDIA improved cardiac function and counteracted against adverse remodeling among AMI rats, which most likely is due to it promoting angiogenesis. Transcriptome analysis by RNA-sequencing found that MUSKARDIA up-regulated cardiac pro-angiogenic genes, particularly growth differentiation factor 15 (GDF15), which was confirmed by RT-qPCR. This up-regulation was also correlated with elevated serum GDF15 levels. In vitro analyses with human umbilical vein endothelial cells found that increased GDF15, stimulated by MUSKARDIA, resulted in enhanced cell migration, proliferation, and tubular formation, all of which were reversed after GDF15 knockdown using a lentiviral vector. Gene Ontology, as well as Kyoto Genes and Genomes enrichment analyses identified calcium signaling pathway as a major contributor to these outcomes, which was verified by Western blot and Cal-590 AM loading showing that transient receptor potential cation channel subfamily V member 4 protein (TRPV4) and intracellular Ca2+ levels increased in accordance with MUSKARDIA-induced GDF15 up-regulation, and decreased with GDF15 knock-down. Therefore, MUSKARDIA may exert its cardioprotective effects via stimulating the GDF15/TRPV4/calcium signaling/angiogenesis axis.

Electroacupuncture reduces fibromyalgia pain by downregulating the TRPV1-pERK signalling pathway in the mouse brain.

BACKGROUND: Acupuncture has been clinically recommended as a method of pain relief by the World Health Organization and is widely used by medical doctors. Fibromyalgia (FM) pain has a complex physiological and psychological origin and can be pharmacologically treated with duloxetine, milnacipran and pregabalin. However, these drugs produce undesirable side effects, such as headaches, nausea and diarrhoea. Acupuncture may serve as an effective alternative treatment for pain relief with few side effects. AIMS: We hypothesised that acupuncture would reduce FM pain by influencing transient receptor potential cation channel subfamily V member 1 (TRPV1) and the downstream phosphorylated extracellular signal-regulated kinases (pERK), which are located in the central thalamus, amygdala and cortex. METHODS: A FM mouse model was established by injecting two doses of acid saline into 32 female C57/B6 mice. The mice were then assigned to different subgroups (n=8 each) and treated with electroacupuncture (EA) or EA sham control. TRPV1 and pERK expression levels were measured using Western blotting and immunohistochemistry. RESULTS: Our results demonstrated that the expression of TRPV1 and pERK in the thalamus, amygdala and somatosensory cortex was normal in the control mice, but significantly increased in FM mice; these FM-induced changes in expression were attenuated by EA. CONCLUSION: Our data suggest that EA can reverse the central sensitisation of the TRPV1-ERK signalling pathway in the mouse brain. Thus, our findings provide mechanistic evidence supporting the potential therapeutic efficacy of EA for treating FM pain.

Capsaicin: Plants of the Genus Capsicum and Positive Effect of Oriental Spice on Skin Health.

BACKGROUND: Capsaicin, the main pungent ingredient in hot chili peppers, causes excitation of small sensory neurons. It also provides the basic pungent flavor in Capsicum fruits. SUMMARY: Capsaicin plays a vital role as an agonist for the TRPV1 (transient receptor potential cation channel, subfamily V, member 1) receptor. TRPV1 is essential for the reduction of oxidative stress, pain sensations, and inflammation. Therefore, it has many pros related to health issue. Activation and positive impact of TRPV1 via capsaicin has been studied in various dermatological conditions and in other skin-related issues. Past studies documented that capsaicin plays a vital role in the prevention of atopic dermatitis as well as psoriasis. Moreover, TRPV1 is also very important for skin health because it acts as a capsaicin receptor. It is found in nociceptive nerve fibers and nonneural structures. It prompts the release of a compound that is involved in communicating pain between the spinal cord nerves and other parts of the body. Key Messages: Here, we summarize the growing evidence for the beneficial role of capsaicin and TRPV1 and how they help in the relief of skin diseases such as inflammation, permeation, dysfunction, atopic dermatitis, and psoriasis and in pain amplification syndrome.

Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice.

The vitamin D receptor (VDR) maintains a balance of plasma calcium and 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH)2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH)2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH)2D3 treatment in mice (2.5 µg/kg ip, singly or q2d × 4). After a single ip dose, plasma 1,25(OH)2D3 peaked at ∼0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH)2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH)2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH)2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH)2D3.