Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms underlying its action are still largely unknown. In this study, we established a mouse model of NAFLD by administering a methionine- and choline-deficient (MCD) diet and selected three acupoints (ST36, CV4, and KI1) or nonacupoints (sham) for needling. We then investigated the effects of acupuncture treatment on the progression of NAFLD and the underlying mechanisms. After two weeks of acupuncture treatment, the liver in the needling-nonapcupoint group (NG) mice appeared pale and yellowish in color, while that in the needling-acupoint group (AG) showed a bright red color. Histologically, fewer lipid droplets and inflammatory foci were observed in the AG liver than in the NG liver. Furthermore, the expression of proinflammatory signaling factors was significantly downregulated in the AG liver. A lipid analysis showed that the levels of triglyceride (TG) and free fatty acid (FFA) were lower in the AG liver than in the NG liver, with an altered expression of lipid metabolism-related factors as well. Moreover, the numbers of 8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic thiobarbituric acid reactive substances (TBARS) were significantly lower in AG mice than in NG mice. In line with these results, a higher expressions of antioxidant factors was found in the AG liver than in the NG liver. Our results indicate that acupuncture repressed the progression of NAFLD by inhibiting inflammatory reactions, reducing oxidative stress, and promoting lipid metabolism of hepatocytes, suggesting that this approach might be an important complementary treatment for NAFLD.

Background: Urinary stones (urolithiasis) have been categorized as kidney stones (renal calculus), ureteric stones (ureteral calculus and ureterolith), bladder stones (bladder calculus), and urethral stones (urethral calculus); however, the mechanisms underlying their promotion and related injuries in glomerular and tubular cells remain unclear. Although lifestyle-related diseases (LSRDs) such as hyperglycemia, type 2 diabetic mellitus, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, and cardiovascular disease are risk factors for urolithiasis, the underlying mechanisms remain unclear. Recently, heat shock protein 90 (HSP90) on the membrane of HK-2 human proximal tubular epithelium cells has been associated with the adhesion of urinary stones and cytotoxicity. Further, HSP90 in human pancreatic and breast cells can be modified by various advanced glycation end-products (AGEs), thus affecting their function. Hypothesis 1: We hypothesized that HSP90s on/in human proximal tubular epithelium cells can be modified by various types of AGEs, and that they may affect their functions and it may be a key to reveal that LSRDs are associated with urolithiasis. Hypothesis 2: We considered the possibility that Japanese traditional medicines for urolithiasis may inhibit AGE generation. Of Choreito and Urocalun (the extract of Quercus salicina Blume/Quercus stenophylla Makino) used in the clinic, Choreito is a Kampo medicine, while Urocalun is a characteristic Japanese traditional medicine. As Urocalun contains quercetin, hesperidin, and p-hydroxy cinnamic acid, which can inhibit AGE generation, we hypothesized that Urocalun may inhibit the generation of AGE-modified HSP90s in human proximal tubular epithelium cells.

Oral mucositis (stomatitis) is a painful condition that affects the mouth lining. Kampo medicines (e.g., Hangeshashinto [Chinese name, Ban-Xia-Xie-Xin-Tang], Orento, and Orengedokuto) have been widely used to treat stomatitis, such as gargling with Hangeshashinto. However, the mechanisms by which Kampo medicines work are not widely understood due to their oral administration and the subsequent digestion, absorption, and metabolization of their components. Stomatitis is associated with advanced glycation end-products (AGEs) in patients with lifestyle diseases, and can be induced by both intra- and extracellular AGEs (blood and dietary AGEs). Various natural products inhibit intracellular AGE generation and suppress cytotoxicity, such as inflammation caused by extracellular AGEs. This review summarizes 19 natural products identified in the Hangeshashinto water extract and 16 natural products identified in the crude drug extract. The data show that several natural products, such as glycyrrhizin, baicalin, 6-shogaol, quercetin, epigallocatechin-3-galate, and genistein, inhibit intracellular AGEs and suppress extracellular AGE inflammation. Furthermore, several natural products in the Hangeshashito water extract can suppress cytotoxicity in stomatitis.

Advanced glycation end-products (AGEs) are associated with the dysfunction of proximal tubular epithelial (PTE) cells in lifestyle diseases. Urinary stones induce cytotoxicity in PTE cells, and various medicines have been developed to mitigate or prevent their generation/accumulation. The leaves of Quercus salicina Blume/Q. stenophylla Makino—used in Japanese folk medicine—contain quercetin, hesperidin, and p-hydroxycinnamic (p-coumaric) acid, which can suppress the cytotoxicity of intra-/extracellular AGEs. This review investigated the effects of quercetin, hesperidin, and p-coumaric acid on PTE cells in terms of their metabolism following oral administration and the associated organs and bacteria. Current evidence indicates that, in PTE cells, non-metabolized quercetin and p-coumaric acid may suppress intra-/extracellular AGE-induced cytotoxicity, whereas the metabolites of quercetin and hesperidin may inhibit the generation of AGEs. However, little is known of the effects of p-coumaric acid metabolites. Quercetin, hesperidin, and p-coumaric acid may collectively suppress the cytotoxicity of intra-/extracellular AGEs in PTE cells. This review on the current paradigm of Q. salicina/Q. stenophylla extract provides a useful baseline for the design of further preclinical and clinical investigations.