Potential of the Novel Slot Blot Method with a PVDF Membrane for Protein Identification and Quantification in Kampo Medicines.

Kampo is a Japanese traditional medicine modified from traditional Chinese medicine. Kampo medicines contain various traditional crude drugs with unknown compositions due to the presence of low-molecular-weight compounds and proteins. However, the proteins are generally rare and extracted with high-polarity solvents such as water, making their identification and quantification difficult. To develop methods for identifying and quantifying the proteins in Kampo medicines, in the current study we employ previous technology (e.g., column chromatography, electrophoresis, and membrane chromatography), focusing on membrane chromatography with a polyvinylidene difluoride (PVDF) membrane. Moreover, we consider slot blot analysis based on the principle of membrane chromatography, which is beneficial for analyzing the proteins in Kampo medicines as the volume of the samples is not limited. In this article, we assess a novel slot blot method developed in 2017 and using a PVDF membrane and special lysis buffer to quantify advanced glycation end products-modified proteins against other slot blots. We consider our slot blot analysis superior for identifying and quantifying proteins in Kampo medicines compared with other methods as the data obtained with our novel slot blot can be shown with both error bars and the statistically significant difference, and our operation step is simpler than those of other methods.

Novel In Vitro Assay of the Effects of Kampo Medicines against Intra/Extracellular Advanced Glycation End-Products in Oral, Esophageal, and Gastric Epithelial Cells.

Kampo medicines are Japanese traditional medicines developed from Chinese traditional medicines. The action mechanisms of the numerous known compounds have been studied for approximately 100 years; however, many remain unclear. While components are normally affected through digestion, absorption, and metabolism, in vitro oral, esophageal, and gastric epithelial cell models avoid these influences and, thus, represent superior assay systems for Kampo medicines. We focused on two areas of the strong performance of this assay system: intracellular and extracellular advanced glycation end-products (AGEs). AGEs are generated from glucose, fructose, and their metabolites, and promote lifestyle-related diseases such as diabetes and cancer. While current technology cannot analyze whole intracellular AGEs in cells in some organs, some AGEs can be generated for 1-2 days, and the turnover time of oral and gastric epithelial cells is 7-14 days. Therefore, we hypothesized that we could detect these rapidly generated intracellular AGEs in such cells. Extracellular AEGs (e.g., dietary or in the saliva) bind to the receptor for AGEs (RAGE) and the toll-like receptor 4 (TLR4) on the surface of the epithelial cells and can induce cytotoxicity such as inflammation. The analysis of Kampo medicine effects against intra/extracellular AGEs in vitro is a novel model.

Pharmacists' perspectives on traditional, complementary, and integrative medicine in Japan with special reference to Kampo medicines: an internet survey with preliminary interviews.

BACKGROUND: Pharmacists guide patients in their use of traditional, complementary, and integrative medicine (TCIM). The present study aimed to evaluate the opinions of Japanese pharmacists regarding TCIM, and to evaluate the usability of the evidence-based Japanese Integrative Medicine (eJIM) website from the pharmacists' point of view. METHODS: We conducted a two-stage, mixed-method study using interviews and an internet-based survey. In-person interviews were conducted with 20 pharmacists working in hospitals, dispensing pharmacies, or retail pharmacies. We analyzed their perspectives on TCIM and the usability of the eJIM. Based on the interviews, questionnaires for an internet survey conducted in February 2019 were developed. RESULTS: In the interviews, 55% of pharmacists acknowledged TCIM as a supportive measure for modern medicine, and 45% responded that TCIM was efficacious. However, pharmacists' evaluation levels of Kampo medicine were high, whereas pharmacists' attitudes towards dietary supplements were primarily negative. There have been various proposals to improve the eJIM, such as highlighting important information and providing more specific information on TCIM in Japan. An internet survey of 365 pharmacists showed that 67.4% were consulted by patients regarding TCIM. Of these TCIM, pharmacists' evaluation levels of Kampo medicines were high. Only 5% of the respondents had visited the eJIM website prior to the survey, and the overall usability score of each web page was high. CONCLUSIONS: Kampo medicines and dietary supplements are common TCIMs that pharmacists use or advise on in Japan. Pharmacists' evaluation levels of Kampo medicine were high, whereas pharmacists' attitudes towards dietary supplements were generally negative.

Kampo medicines for supportive care of patients with cancer: A brief review.

BACKGROUND: Kampo medicines, which are standardized traditional Japanese herbal medicines, have been tried to support patients with cancer. METHODS: Randomized controlled trials on the use of Kampo medicines for cancer supportive care and the descriptions of Kampo medicines in clinical practice guidelines were reviewed. RESULTS: Kampo medicines potentially ameliorate refractory symptoms in cancer patients. For example, hochuekkito, juzentaihoto, and ninjin'yoeito seem to be efficacious for fatigue/general malaise. Potential use of rikkunshito for anorexia/cancer cachexia and goshajinkigan for peripheral neuropathy is proposed from small numbers of randomized controlled trials in addition to basic research. The number of clinical practice guidelines which contain descriptions of Kampo medicines is increasing in general, but only a few in the area of cancer supportive care. CONCLUSION: Kampo medicines potentially play some roles in preventing or ameliorating side effects of anticancer agents. Supportive care with Kampo medicines for patients with cancer might lead to physical, mental, and nutritional improvement.

Role of Kampo Medicine in Modern Cancer Therapy: Towards Completion of Standard Treatment.

Kampo Medicine is a traditional Japanese medicine and is well integrated with modern medicine. Anticancer agents are highly developed, and evidence regarding standard treatment has accumulated. Kampo Medicine helps support patients with cancer who lack vital energy and feel cold. Cancer chemotherapy is associated with adverse reactions that are refractory to modern therapy, such as anorexia, general malaise/fatigue, and peripheral neuropathy. Recently, evidence of the effectiveness of Kampo Medicines for these symptoms has been reported in randomized controlled trials (RCTs). The Japan Society for Oriental Medicine celebrated the first 20 years of its evidence-based medicine (EBM) committee in June 2021. The activities of this committee include publication of the Evidence Reports of Kampo Treatment, which contains RCTs and meta-analyses, including RCTs on cancer supportive care. Evidence is accumulating for hangeshashinto for mucositis, rikkunshito for anorexia, goshajinkigan and ninjin'yoeito for peripheral neuropathy, hochuekkito for general malaise/fatigue, and shakuyakukanzoto for myalgia/arthralgia. However, additional evidence and further clinical trials are needed. Supportive care with Kampo Medicine increases the likelihood of completing standard treatment for cancer.

Physician perspectives on traditional, complementary, and integrative medicine and the national evidence-based Japanese integrative medicine information website: A mixed-method study.

BACKGROUND: The evidence-based Japanese integrative medicine (eJIM) website was launched by the Japanese government in 2014 to provide information on integrative medicine to the general public and physicians. While Japanese physicians discourage the use of traditional, complementary, and integrative medicine (TCIM), there are very few reports that explore this issue. We aimed to understand the attitudes of Japanese physicians towards TCIM and evaluate the usability of the eJIM website according to physicians. METHODS: We conducted a two-staged, mixed-method study with interviews and an internet-based survey. Face-to-face interviews were conducted with 12 physicians who worked for large-scale hospitals in two different areas of Japan. We assessed their understanding of TCIM and the usability of the eJIM website. Based on the interviews, the internet survey was developed and was conducted in February 2019. RESULTS: In the interviews, 12 physicians provided their opinion on TCIM and highlighted important areas, such as increasing the resources available for patients, and ensuring more information on TCIM is available. The internet survey of 231 physicians showed that 35% of the physicians used or advised on TCIM in clinical practice. Kampo medicines (87.8%) and dietary supplements (24.7%) were common. The physicians did not use TCIM primarily because of concerns regarding its efficacy, safety, and cost. Most physicians were not aware of which TCIM their patients used. CONCLUSION: Physicians in Japan may not have comprehensively understood TCIM and do not actively use TCIM. The eJIM website could help physicians to gain a better understanding of TCIM if improvements are made.

Acupuncture improved lipid metabolism by regulating intestinal absorption in mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), in which abnormal lipid metabolism plays an important role in disease progression, has become a pandemic. Abnormal lipid metabolism, for example an increased fat intake, has been thought to be an initial factor leading to NAFLD. The small intestine is the main site of dietary lipid absorption. A number of clinical trials have shown that acupuncture has positive effects in the regulation of lipid metabolism, which is closely associated with the progression of NAFLD. We therefore hypothesized that, acupuncture can improve the conditions of NAFLD by regulating intestinal absorption of lipid. AIM: To study the role of acupuncture treatment in the improvement of metabolic syndrome secondary to NAFLD by mouse model. METHODS: 8-wk-old male C57BL/6J mice were fed a methionine- and choline-deficient diet for 3 wk. Then, all mice were separated randomly into acupoints group (AG) or non-acupoints group (NG) with high fat diet feeding. Needling treatment was performed at Zu san li, Guan yuan and Yong quan acupoints as acupuncture treatment to AG mice while non-acupoints place to NG mice. Finally, mice were anesthetized with an injection of ketamine-medetomidine and euthanized by exsanguination. RESULTS: An apparent improvement of obesity was found in AG mice after acupuncture treatment. In AG mice, the body weight was much lower (22.6 ± 1.2 g vs 28.1 ± 1.0 g, P < 0.005) in comparison to NG mice. The length of small intestine in AG mice was significantly shorter (26.7 ± 2.3 cm vs 32.7 ± 2.7 cm, P < 0.005). A large amount of chyme was observed in the lumen of the AG small intestine. The expression of microsomal triglyceride transfer protein, apolipoprotein B and apolipoprotein C2 was downregulated. Triacylglycerols (TGs), total cholesterol and nonesterified fatty acid (NEFA) levels of the small intestinal tissue were significantly higher in AG mice, but the serum TGs and NEFA levels were reduced in AG mice. CONCLUSION: These results indicate that acupuncture at Zu san li, Guan yuan and Yong quan suppressed lipid absorption by downregulating the expression of apolipoproteins in the small intestine.

Prophylactic efficacy of ninjin'yoeito for oxaliplatin-induced cumulative peripheral neuropathy in patients with colorectal cancer receiving postoperative adjuvant chemotherapy: a randomized, open-label, phase 2 trial (HOPE-2).

PURPOSE: Peripheral neuropathy (PN) is an intractable side effect of oxaliplatin, with no effective prophylaxis so far. Ninjin'yoeito (NYT), a Kampo medicine, is protective against oxaliplatin-induced neuronal cell injury in vitro and ameliorates oxaliplatin-induced PN in vivo. Thus, this randomized controlled trial was aimed at clarifying NYT's prophylactic effect for oxaliplatin-induced cumulative PN. METHODS: 52 patients with colorectal cancers of pathological stage 3 received postoperative adjuvant chemotherapy with the CapeOX regimen: eight cycles of capecitabine (2400 mg/m2) plus oxaliplatin (130 mg/m2) at 3-week intervals. They were randomly assigned to NYT administration and non-administration groups. NYT (9.0 g/day) was administered from day 1 of cycle 1 in the NYT group. The NYT was administered orally daily throughout each cycle. The primary endpoint was the grade of cumulative PN at the end of eight cycles. The secondary endpoints included relative dose intensity (RDI) of oxaliplatin, recurrence-free survival (RFS), and overall survival (OS). RESULTS: 40 patients (n = 20 in both groups) completed 8 chemotherapy cycles. The incidence of grade 2 or greater cumulative PN at the 8th chemotherapy cycle was significantly lower in the NYT group (2/20, 10.0%) than in the control group (11/20, 55.0%, P < 0.01). RDI of oxaliplatin was significantly higher in the NYT group than in the control group (P = 0.02). RFS and OS were better in the NYT group than in the control group, but the difference was not significant. CONCLUSIONS: NYT may reduce the incidence of oxaliplatin-induced cumulative PN and facilitate maintenance of the CapeOX dosing regimen.

Perspectives on the Use of Ninjin'yoeito in Modern Medicine: A Review of Randomized Controlled Trials.

BACKGROUND: Ninjin'yoeito (NYT), a traditional Japanese (Kampo) medicine that originates from China, has been used to treat qi and blood deficiency based on its original concept. Kampo medicine has been widely used to treat many conditions and disorders combined with western medicine or Kampo medicine alone in modern situation. AIMS: We reviewed randomized controlled trials (RCTs) of NYT and discussed various standpoints regarding its use in modern situation. METHODS: We searched PubMed, Cochrane Library, and Evidence Reports of Kampo Treatment (EKAT) for articles written in English, and Ichushi, J-Stage, and EKAT for those written in Japanese. Articles published before January 1, 2019, were retrieved using the keywords "ninjinyoeito" and "ninjin'yoeito," and RCTs were selected from these extracted articles. RESULT: Of 734 articles, 13 were RCTs, 46 were non-RCTs or studies of other designs, 15 were case reports, and 36 were experimental studies using NYT. NYT was evaluated for its use as a treatment for cancer and related conditions, refractory blood diseases and conditions, and otorhinolaryngologic symptom in 13 RCTs. Based on the use of Kampo medicine in modern situation called as Yasui's classification, 10 of 13 RCTs were categorized as "the side effects of Western medicinal treatment are mitigated when combined with Kampo treatment" and the remaining 3 were categorized as "treatment effect of Kampo medicine is increased in combination with standard Western medicinal treatment." Conclusion. Several studies demonstrated the efficacy of NYT in refractory diseases and other conditions, and the accompanied side effects of treatment with western medicine.

[Complementary and Alternative Medicine for Breast Cancer Patients: An Overview of Systematic Reviews].

The application of systematic review (SR) has been increased rapidly in the field of cancer treatment. Complementary and alternative medicine (CAM) for cancer is no exception. The aim of this review is to evaluate and summarize systematic reviews on the CAM use in breast cancer patients. Search sources were Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR), and PubMed. In addition, we assessed the quality of SR with the Assessing the Methodological Quality of Systematic Reviews (AMSTAR). This review did not consider control groups and outcomes. Thirty-four SRs met a set of criteria. According to interventions, there were twenty SRs which included yoga, acupuncture, and herbal medicines. Meta-analysis of 19 out of 34 reviews showed the followings: (1) acupuncture had a beneficial effect on the frequency of hot flushes, (2) yoga had a beneficial effect on depression and health-related QOL, (3) mindfulness-based stress reduction (MBSR) had a beneficial effect on anxiety and depression, (4) combination of herbal medicine and chemotherapy synergistically improved clinical outcomes, (5) acupuncture did not show significant effect on the severity of hot flushes and cancer-related pain, (6) yoga was unable to be confirmed as having an effect on cancer-related pain and physical well-being. Given the results of AMSTAR, 9 out of 34 reviews were of high quality and 3 reviews were deemed to be of low quality. In conclusion, since most SRs were at moderate or high quality levels, CAM could be helpful for treating specific symptoms related to breast cancer.

Efficacy of daikenchuto, a traditional Japanese Kampo medicine, for postoperative intestinal dysfunction in patients with gastrointestinal cancers: meta-analysis.

BACKGROUND: The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. METHODS: Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto ( https://mpdb.nibiohn.go.jp/stork ) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). RESULTS: We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were - 0.43 (95% CI: - 0.77 to - 0.09) days for the time to first postoperative flatus, - 0.29 (95% CI: - 0.59 to 0.01) days for the time to first postoperative BM, and - 0.95 (95% CI: - 1.70 to - 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35-1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. CONCLUSION: As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared.

The utilization of complementary and alternative medicine in Taiwan: An internet survey using an adapted version of the international questionnaire (I-CAM-Q).

BACKGROUND: In Taiwan, numerous studies have been conducted to investigate the use of complementary and alternative medicine (CAM). However, most of them focused on specific diseases or the use of particular methods. Therefore, the results of those studies were quite different and difficult to compare with those of studies from other countries. The International CAM Questionnaire (I-CAM-Q), meanwhile, is a unified tool that can provide comparable results for studies conducted worldwide. Thus, the aim of this study was to discover the proportions of people in Taiwan receiving CAM treatments from different types of health care providers by using an adapted version of I-CAM-Q (I-CAM-QT). METHODS: I-CAM-QT was developed by translating the Korean version of I-CAM-Q (I-CAM-QK) into traditional Chinese language because of the similarity of CAM usage and doctor licensing system. This study had two stages: the first was a pretest survey used to adjust the questionnaire, while the second was an internet-based survey used to collect data from the community. RESULTS: Of the 1200 survey respondents, 37% and 37.7% were prescribed or advised to use Chinese herbal medicine (CHM) by Western medicine (WM) physicians and traditional Chinese medicine (TCM) doctors, respectively. Other than CHM, dietary supplements and massage were the forms of CAM most commonly prescribed or recommended by WM physicians or TCM doctors. Overall, walking and relaxation techniques were the most commonly used self-help practices (used by 61.9% and 40.4% of the respondents, respectively). Additionally, 70.3% of the respondents had used at least one kind of dietary supplement in the past 12 months. CONCLUSION: Regarding the utilization of CAM in Taiwan, this internet-based survey revealed that CHM, dietary supplements, and massage were the types of CAM most commonly prescribed or recommended by WM physicians or TCM doctors.

Internet survey on the provision of complementary and alternative medicine in Japanese private clinics: a cross-sectional study.

OBJECTIVE: Although the use of complementary and alternative medicine (CAM) by the general population has been surveyed previously, the provision of CAM by Japanese physicians in private clinics has not been studied. Universal health insurance system was established in Japan in 1961, and most CAMs are not on the drug tariff. We aimed to clarify the current status of CAM provided by physicians at private clinics in Japan. METHODS: We conducted an internet survey on 400 directors/physicians of private clinics nationwide on the provision of CAM from February 6 to February 10, 2017. Survey items included attributes of subjects, presence/absence of sections or facilities for provision of CAM, proportions of health insurance coverage for medical practices, and source of information. Private clinic was defined as a clinic run by one physician, with less than 20 beds. RESULTS: Commonly provided CAMs were Kampo (traditional Japanese herbal) medicines (34.8%) and supplements/health foods (19.3%). CAMs on the drug tariff were provided in 46.5% of cases at the clinics, but only 16.5% of cases were provided CAMs which were not on the drug tariff, at different neighboring facilities. Among different specialties, Kampo medicines were prescribed at obstetrics/gynecology (54.0%), orthopedics (44.4%), and dermatology (43.0%). Clinics not providing any CAM accounted for 53.5%. With regard to health insurance coverage, 96.8% of the clinics provided only or mainly health services on the universal national health insurance tariff (29.8% and 67.0%, respectively). CONCLUSION: Kampo medicines represent the most commonly used CAM in private clinics in Japan, and universal national health insurance coverage is considered to be the reason for the high rate of their use.

Use of Complementary and Alternative Medicine in Japan: A Cross-sectional Internet Survey Using the Japanese Version of the International Complementary and Alternative Medicine Questionnaire.

INTRODUCTION: Although there have been several national survey studies on complementary and alternative medicine (CAM) use in Japan, previous studies have not been compared with investigations conducted in other countries. An international CAM questionnaire known as I-CAM-Q was developed through a two-day international workshop in 2006. The purpose of this study was to investigate the use of CAM by the general Japanese population using a modified version of the I-CAM-Q for the Japanese (I-CAM-QJ). METHODS: We developed the I-CAM-QJ to conduct an internet survey of 3,208 participants from the general population of Japan in February 2016. The respondents included 1,592 males (49.6%), 1,348 university graduates (38.8%), 1,105 individuals in good health (34.4%), and 1,028 individuals with long-term illness or disability (32.0%). RESULTS: Of the 3,208 respondents, 411 participants reported CAM use during the past 12 months (12.8%). The following therapies and products were used: Kampo medicines (over-the-counter Kampo medicines: 15.7%; prescribed Kampo medicines: 15.4%), dietary supplements 11.8%, massage services 3.9%, and physical therapy 3.5%. Regarding the use of self-care methods during the last 12 months, the following methods and products were used: bath salts 25.8% and walking 25.3%. CONCLUSIONS: An internet survey on CAM use by the general Japanese population with a modified I-CAM-Q (I-CAM-QJ) revealed that Kampo medicines and dietary supplements were the most commonly used CAMs in Japan.

Usability of the evidence-based Japanese integrative medicine (eJIM) information site: analysis with focus group discussion and internet survey on the general population.

BACKGROUND: The information site for evidence-based Japanese Integrative Medicine (eJIM) was launched by the Japanese Ministry of Health, Labour and Welfare to enable patients, medical staff, and others to obtain appropriate information, but it has not been objectively evaluated by users. The present study aimed to assess the usability of the eJIM website from the viewpoint of the general population. METHODS: We held a focus group discussion with 12 persons in November 2016, conducted an Internet survey of 1107 people (general population) in February 2017, and assessed their understanding of basic concepts of complementary and alternative medicine and usefulness of the contents after browsing the eJIM website. Levels of functional, communicative, and critical health literacy were also assessed. RESULTS: Most patients had never visited the eJIM website, because basic terms such as "integrative medicine" and "evidence" were not fully understood. Most overseas information in English was difficult to understand for the general Japanese population, although approximately 50% of the information was translated into Japanese. The degree of appropriate responses depended on health literacy level. CONCLUSION: The usability of eJIM website was low, because the currently available information did not meet the needs of the general population. Moreover, simpler expressions and visual tools would help the general population to understand the website contents more easily. A further survey that considers cultural and quantitative perspectives is warranted.

An assessment of the use of complementary and alternative medicine by Korean people using an adapted version of the standardized international questionnaire (I-CAM-QK): a cross-sectional study of an internet survey.

BACKGROUND: In Korea, there are two types of medical doctors: one practises conventional medicine (hereafter called a physician), and the other practises traditional medicine (hereafter called a Korean medical doctor). This study aimed to compare the provision of complementary and alternative medicine (CAM) by these providers to CAM use per self-judgement in Korea. METHODS: We analysed 1668 Korean people via an internet survey with the Korean adopted version of the I-CAM-Q, namely, the International Questionnaire to measure use of CAM, to understand whether respondents used CAM based either on a prescription or advice from a physician or a Korean medical doctor or on self-judgement. RESULTS: In the previous 12 months, the proportions of respondents who were treated by a physician, who were treated by a Korean medical doctor and who were not treated by anyone were 67.9, 20.7 and 14.2%, respectively. Among the respondents who received CAM based on a prescription or advice from a physician, traditional Korean medicine practices and dietary supplements were commonly used; only a small percentage used other CAM therapies. Respondents who received CAM based on a prescription or advice from a Korean medical doctor showed similar results. Acupuncture and moxibustion, traditional Korean medicines (decoction), or cupping were more commonly used. Korean traditional medicines as over-the-counter (OTC) drugs were more commonly used by respondents who received CAM therapy based on a prescription or advice from a physician than by those who received CAM therapy based on a prescription or advice from a Korean medical doctor. A total of 74% of the responders used any CAM by self-judgement in the previous 12 months. CONCLUSIONS: For the use of CAM in Korea, in addition to the Korean traditional medical care provided by Korean medical doctors, general physicians advised people regarding Korean traditional medical care and dietary supplements.

Effect of ninjin'yoeito and ginseng extracts on oxaliplatin-induced neuropathies in mice.

Oxaliplatin (L-OHP) is a platinum-based anticancer agent used to treat various types of cancer. It frequently causes acute and chronic peripheral neuropathies, such as cold allodynia and mechanical hyperalgesia. Ninjin'yoeito (NYT) is a formula used in traditional Japanese Kampo medicine to improve recovery from diseases and other medical disorders. We previously reported that treatment with a boiling-water extract of NYT prevented L-OHP-induced damage to neurite-like outgrowths from differentiated PC12 cells. The objectives of the present study were to evaluate the in vivo effects of NYT on L-OHP-induced neuropathic pain in mice and identify the active ingredients in NYT. Treatment with NYT extract significantly ameliorated both cold allodynia and mechanical hyperalgesia induced by L-OHP. While L-OHP treatment suppressed neurite outgrowths from primary dorsal root ganglion cells in vitro, NYT extract blocked this suppression in a concentration-dependent manner. Among the herbal components of NYT, the extract of ginseng (Panax ginseng roots) showed a protective effect against neurite damage induced by L-OHP, and one of its active ingredients was identified as ginsenoside Rg3. Ginseng extract partially relieved L-OHP-induced neuropathic pain in mice. Our results suggest that NYT could be an attractive agent for treating L-OHP-induced neuropathic pain, and that the active ingredient of NYT may be ginseng.

Standards of Reporting Kampo Products (STORK) in research articles.

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose the use of the Standards of Reporting Kampo Products (STORK) website, http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

Ninjin'yoeito and ginseng extract prevent oxaliplatin-induced neurodegeneration in PC12 cells.

Ninjin'yoeito (NYT) is a formula of Japanese traditional kampo medicine composed of 12 crude drugs, and is designed to improve the decline in constitution after recovery from disease, fatigue, anemia, anorexia, perspiration during sleep, cold limbs, slight fever, chills, persistent cough, malaise, mental disequilibrium, insomnia, and constipation. Oxaliplatin (L-OHP) is a platinum-based anticancer drug used to treat colorectal, pancreatic, and stomach cancers. However, it often causes acute and chronic peripheral neuropathies including cold allodynia and mechanical hyperalgesia. In this study, we investigated the preventive effects of NYT on neuronal degeneration caused by L-OHP using PC12 cells, which are derived from the rat adrenal medulla and differentiate into nerve-like cells after exposure to nerve growth factor. L-OHP treatment decreased the elongation of neurite-like projection outgrowths in differentiated PC12 cells. When PC12 cells were treated with NYT hot water extract, neurodegeneration caused by L-OHP was significantly prevented in a concentration-dependent manner. Among the 12 crude drugs composing NYT, the extract of Ginseng (the root of Panax ginseng) exhibited the strongest preventive effects on neurodegeneration in differentiated PC12 cells. By activity-guided fractionation, we found that the fraction containing ginsenosides displayed preventive activity and, among several ginsenosides, ginsenoside F2 exhibited significant preventive effects on L-OHP-induced decreases in neurite-like outgrowths in differentiated PC12 cells. These results suggest that NYT and ginseng are promising agents for preventing L-OHP-induced neuropathies and present ginsenoside F2 as one of the active ingredients in ginseng.