The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.

BACKGROUND: Trauma and sepsis both increase the risk for secondary infections. Injury mobilizes mitochondrial (MT) danger-associated molecular patterns (mtDAMPs) directly from cellular necrosis. It is unknown, however, whether sepsis can cause active MT release and whether mtDAMPs released by sepsis might affect innate immunity. METHODS: Mitochondrial release from human monocytes (Mo) was studied after LPS stimulation using electron microscopy and using fluorescent video-microscopy of adherent Mo using Mito-Tracker Green (MTG) dye. Release of MTG⁺ microparticles was studied using flow cytometry after bacterial stimulation by size exclusion chromatography of supernatants with polymerase chain reaction (PCR) for mitochondrial DNA (mtDNA). Human neutrophil (PMN), chemotaxis, and respiratory burst were studied after PMN incubation with mtDNA. RESULTS: LPS caused Mo to release mtDAMPs. Electron microscopy showed microparticles containing MT. mtDNA was present both in microvesicles and exosomes as shown by PCR of the relevant size exclusion chromatography bands. In functional studies, PMN incubation with mtDNA suppressed chemotaxis in a dose-dependent manner, which was reversed by chloroquine, suggesting an endosomal, toll-like receptor-9–dependent mechanism. In contrast, PMN respiratory burst was unaffected by mtDNA. CONCLUSION: In addition to passive release of mtDAMPs by traumatic cellular disruption, inflammatory and infectious stimuli cause active mtDAMP release via microparticles. mtDNA thus released can have effects on PMN that may suppress antimicrobial function. mtDAMP-mediated “feed-forward” mechanisms may modulate immune responses and potentially be generalizable to other forms of inflammation. Where they cause immune dysfunction the effects can be mitigated if the pathways by which the mtDAMPs act are defined. In this case, the endosomal inhibitor chloroquine is benign and well tolerated. Thus, it may warrant study as a prophylactic antiinfective after injury or prior sepsis.

The enormous library of natural products and herbal medicine prescriptions presents endless research avenues. However, the lack of research evidence and trials on cancer-induced cachexia limit the therapeutic potential of natural products. Cancer-induced cachexia is a systemic wasting syndrome characterized by continuous body weight loss with skeletal muscle and adipose tissue atrophy. Cancer cachexia is a problem in itself and reduces the quality of life by lessening the treatment efficacy of anticancer drugs. This review summarizes single natural product extracts for cancer-induced cachexia, not compounds derived from natural products and herbal medicine prescriptions. This article also discusses the effect of natural products on cachexia induced by anticancer drugs and the role of AMPK in cancer-induced cachexia. The article included the mice model used in each experiment to encourage researchers to utilize animal models for research on cancer-induced cachexia in the future.

AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that serves as a central metabolic sensor and regulator of energy balance at both the cellular and organismal levels

Paclitaxel-induced neuropathic pain (PINP) is a serious adverse effect of chemotherapy. Dendrobii caulis (D. caulis) is a new food source used as herbal medicine in east Asia. We examined the antinociceptive effects of D. caulis extract on PINP and clarified the mechanism of action of transient receptor potential vanilloid 1 receptor (TRPV1) in the spinal cord. PINP was induced in male mice using multiple intraperitoneal injections of paclitaxel (total dose, 8 mg/kg). PINP was maintained from D10 to D21 when assessed for cold and mechanical allodynia. Oral administration of 300 and 500 mg/kg D. caulis relieved cold and mechanical allodynia. In addition, TRPV1 in the paclitaxel group showed increased gene and protein expression, whereas the D. caulis 300 and 500 mg/kg groups showed a significant decrease. Among various substances in D. caulis, vicenin-2 was quantified by high-performance liquid chromatography, and its administration (10 mg/kg, i.p.) showed antinociceptive effects similar to those of D. caulis 500 mg/kg. Administration of the TRPV1 antagonist capsazepine also showed antinociceptive effects similar to those of D. caulis, and D. caulis is thought to exhibit antinociceptive effects on PINP by modulating the spinal TRPV1.

Obesity is a chronic complex disease defined by excessive adiposity that impairs health