"Oketsu", or stagnant blood syndrome, is one of the important pathological concepts in therapy with Kampo formula and drugs. Here we show the effectiveness of our previously developed in vivo assay system for the evaluation of such drugs. The assay system measures blood flow in the microcirculation of the mouse tail after injection of hen-egg white lysozyme (HEL). The results showed the effectiveness of Kampo formula and crude drugs clinically used to treat "oketsu", while little effect was found with drugs used for other purposes. These results indicated the effectiveness of the method for screening drugs aimed at "oketsu" treatment.
Abdominal palpation is a necessary technique, particular to Japanese Kampo medicine, based on the theory that physiological changes in illness will manifest themselves in the abdomen. Because this technique is used widely in clinical practice for all kinds of conditions, a suitable way of teaching this technique to doctors is called for. To this end, we have developed an abdominal palpation educational simulator, which we call the Fukushin Simulator, consisting of 6 abdominal models exhibiting the typical disease patterns of excessive strain of abdominal muscles (Fukuchokukinkincho), stiffness and rigidity below the heart (Shinkahiko), fullness in the chest and hypochondrium (Kyokyokuman), lower abdominal fullness (Shofukukoman), lower abdominal numbness (Shofukufujin), and abdominal fluid congestion (Shinkabushinsuion). Fourteen Kampo educators in medical faculties in Japan tested the models and then responded to a questionnaire. The results show that, while abdominal fluid congestion was considered to be unsatisfactory in its current form, the other 5 models were all considered to be satisfactory. Evaluators' comments included advice on specific points that could be improved and ideas for future directions, along with opinions to the effect that this simulator could be of great use as an educational tool. In this study, 85.7% of respondents expressed interest or great interest in the simulator, while 78.6% considered it useful or very useful, leading us to believe that it may have a large role to play in educational settings.
Kampo formulations are widely used in the treatment of many inflammatory diseases, including ulcerative colitis. It has been reported that the herbal compound, orengedokuto (OGT), as well as one of its herbal components, a Scutellariae Radix, was able to suppress inflammation in a mouse model of DSS-induced colitis. However, there have been no studies of the effects of any other Kampo formulations that may have direct anti-inflammatory activity in this model. Furthermore, there is no available information regarding the effects of Kampo medicines that have been formulated with omission of a single specific herb. In this study, the anti-inflammatory activity of thirteen Kampo formulations was screened in a DSS-induced murine colitis model. We observed suppression of the shortening of the colon and a decrease in MPO activity, which we believe to be due to the anti-inflammatory activity of saireito (SRT). In addition, we investigated the anti-inflammatory activity of shosaikoto (SST) and goreisan (GRS), which are the two components of SRT. Neither SST nor GRS alone showed anti-inflammatory activity in this model, indicating that the combination of these two compounds is necessary for the anti-inflammatory activity of SRT. Finally, we examined whether SRT retained its anti-inflammatory properties after various specific herbs were eliminated from the formulation. Unlike OGT, the anti-inflammatory activity of SRT was still present after removal of Scutellariae Radix from the formulation. Alternatively, SRT that lacked Bupleuri Radix did not retain any anti-inflammatory activity. These results imply that the anti-inflammatory activity of SRT on DSS-induced murine colitis is dependent on the inclusion of Bupleuri Radix or the combination between Bupleuri Radix and other herbs.
Bakumondoto is empirically used to treat to dry mouth (xerostomia) associated with salivary gland dysfunction. Salivary glands are supplied with nerve fibers that contain neruopeptides, such as substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). These neuropeptides are important modulators of salivation. We studied the effect of bakumondoto on substance P-, CGRP-, VIP-like immunoreactive substances (IS) in saliva and plasma taken from healthy subjects. Bakumondoto (18.0 g) or placebo was orally administered to five healthy males. Saliva and blood samples were taken before, and at 20-240 min after administration, followed by the extracting procedure, and submitted to a highly sensitive enzyme immunoassay system for neuropeptides. A single oral administration of bakumondoto caused significant increases in saliva substance P- and CGRP-IS levels compared with placebo. And this medicine tended to raise saliva volume. In this study, we concluded bakumondoto might affect substance P and CGRP locally in the salivary gland and the elevated levels of these neuropeptides might stimulate production of saliva. Also, the monitoring of saliva and plasma neuropeptide levels might be able to predict the pharmacologic effects of bakumondoto.
In order to evaluate the possibility of Kampo medicines causing pharmacokinetic drug-drug interactions, the effects of 3 Kampo medicines (rikkunshito, yokukansan and boiogito) on the activities of cytochrome P450 (CYP) and P-glycoprotein (P-gp) were investigated in a mouse in vivo study using triazolam and digoxin, respectively, as probe substrates. A significant increase in the plasma triazolam concentration was observed by co-administration of ketoconazole, a Cyp3a inhibitor, whereas none of the Kampo medicines tested showed any significant effects on triazolam pharmacokinetics in mice. Similarly, plasma concentration of digoxin was significantly elevated by quinidine co-administration, while unaffected by any of the Kampo medicines investigated. These findings indicate that rikkunshito, yokukansan and boiogito are unlikely to affect the pharmacokinetics of co-administered drugs which are substrates of CYP3A and/or P-gp.
Oxaliplatin (L-OHP) in combination with infusional 5-fluorourasil / Leucovorin (FOLFOX) has emerged as the treatment of choice for advanced, recurrent colorectal cancer, and its dose-limiting adverse effect is sensory neurotoxicity. We administered ogikeishigomotsuto (OKG: traditional herbal medicine, Kampo) to a patient with recurrence colon cancer with modified FOLFOX6(mFOLFOX6), who subsequently demonstrated clinical improvement of L-OHP-induced neuropathy. A 59-year-old man with recurrent colon cancer was administered mFOLFOX6. During cycles 4, he complained of paresthesia in the distal extremities, which had been induced by L-OHP. To reduce the neurotoxicity of L-OHP, OKG was administered together along with the anticancer agents starting the 7th cycle. The severities of neurotoxicity before and after administration OKG were grade 2 and grade 1 based on the neurotoxicity criteria of DEBIOPHARM (DEB-NTC), respectively. This observation suggests that OKG may be useful agent to reduce or prevent chronic cumulative neurotoxicity due to L-OHP.