Ghrelin Enhancer, the Latest Evidence of Rikkunshito

Abstract

Rikkunshito is a Japanese herbal medicine (Kampo) that has been attracting attention and researched by many researchers not only in Japan but also worldwide. There are 214 rikkunshito articles that can be searched on PubMed by August 2021. The reason why rikkunshito has attracted so much attention is due to an epoch-making report (Gastroenterology, 2008) discovered that rikkunshito promotes the secretion of the orexigenic peptide ghrelin. Since then, many researchers have discovered that rikkunshito has a direct effect on the ghrelin receptor, GHS-R1a, and an effect of enhancing the ghrelin signal to the brain. Additionally, a lot of evidence that rikkunshito is expected to be effective for various gastrointestinal diseases have also been demonstrated. Numerous basic and clinical studies have suggested that rikkunshito affects (i) various discomforts caused by anticancer drugs, gastroesophageal reflux disease, functional dyspepsia, (ii) various stress-induced anorexia, (iii) hypophagia in the elderly, and (iv) healthy lifespan. In this review, as one who discovered the ghrelin enhancer effect of rikkunshito, we will review the research of rikkunshito so far and report on the latest research results.

The Role of Autophagy and Pyroptosis in Liver Disorders

“…It is synthesized from gastric mucosa and secreted into the blood. There are two main forms: acylated ghrelin and deacylated ghrelin [ 53 , 54 ]. The increasing evidence indicates that ghrelin plays an important role in NAFLD [ 55 , 56 ].…”

Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment

“…ISL is not only detected after the oral administration of TJ-43, but a comparable amount of ISL is also shown in plasma and brain distribution, especially compared with an ISL (5 mg~50 mg/kg) single treatment [94]. Magomi et al suggest that ISL is one of the most important active components in TJ-43, acting as an antagonist to both CRF receptor 1 (CRFR1) and serotonin 2C receptor (5-HT2CR) in order to reduce ghrelin secretion, which further improves stressinduced anorexia [94,95,99]. In addition, several multi-center, double-blinded, randomized placebo-controlled studies were conducted to examine its effect with regard to improvements in upper GI disorders, such as dyspepsia [100][101][102][103].…”

“…Even with a standard treatment, a three-drug combination of a 5-HT3 receptor antagonist, a neurokinin-1 receptor antagonist, and dexamethasone (as an aprepitant regimen) show only a 60~80% mitigation of CINV [107]. Seeking further improvement in CINV, some clinical studies recommend the co-administration of TJ-43 as an effective option for breakthrough CINV, as TJ-43 also acts as an antagonist at the 5-HT2B/C, 5-HT3 receptors and the ghrelin receptor [95,99,[108][109][110]. TJ-43 combined with chemotherapy is shown to prevent CINV in esophagus, gastric, lung, cervical, and corpus cancer patients [111][112][113][114].…”

Research Progress of Liujunzi Decoction in the Treatment of Tumor-Associated Anorexia

“… 10 Japanese scholars have found through experiments that cutting off the vagus nerve of rats can reduce the level of acylated ghrelin in plasma, and cisplatin can further reduce the level of acylated ghrelin and cause anorexia. 19 , 20 Subsequently, the administration of ghrelin in rats can improve the reduction of food intake caused by cisplatin. Peripheral factor ghrelin signaling pathway is the most studied in CIA, and GDF-15 related pathway has gradually entered scholars’ vision.…”

“…In 2008, an epoch-making study by Japanese scholars found that Rikkunshito could improve appetite in a cisplatin-induced anorexia model in rats by promoting the secretion of ghrelin, which immediately attracted the attention and research of a large number of scholars. 19 , 20 Clinical study found that LJZD and modified LJZD improved tumor-associated anorexia effectively. 18 , 21–33 A number of animal experiments have also proved that this prescription has the efficacy of preventing and treating tumor-associated anorexia.…”