Experience of Kampo Treatment for Chronic Plantar Fasciitis / 日本東洋医学雑誌

We studied five untreated patients with plantar fasciitis, 15 chronic cases treated only with Western medicine (non-Kampo group), and 15 chronic cases treated with Kampo in addition to Western medicine (Kampo group). There was no difference in age and pain VAS at the first visit among the three groups. All the non-treated cases were improved with conventional treatment and the duration of treatment was short. In the case of patients who did not respond well to the initial treatment in our department, Kampo medicine was started from three months after the first visit. Therefore, there were more refractory cases in the Kampo group, with poor pain VAS at the last observation and a long treatment period. Among them, two cased were effective in combination with yokuininto and tsudosan, one case was yokuininto only, and one case was combination of yokuininto, tsudosan and keishibukuryogankayokuinin. Sokeikakketsuto used in three patients was not effective. Thus, chronic planter fasciitis may include physiology of not only wind-dampness, cold, and blood deficiency but also qi stangnation and blood stasis.

Effectiveness of Makyoyokukanto Combined with Powdered Cinnamon bark and Processed Aconite Root for Chronic Sciatica / 日本東洋医学雑誌

Chronic sciatica is one of the neuropathic pains which assumed to be effective for pregabalin. However, a recent double-blind placebo-controlled trial reported that pregabalin was no more effective than placebo in patients with acute or chronic sciatica. We retrospectively investigated the effect of Kampo medicine including makyoyokukanto extracts combined with powdered cinnamon bark and processed aconite root (makyoyokukanto plus) which were administered to 14 cases with chronic sciatica in the past year. The efficacy of Kampo medicine for lower leg pain relief was assessed using NRS (numerical rating scale). It was effective in 11 of 14 cases (79%, 6 males and 5 females, the mean age : 69), and not effective in 3 of 14 cases (21%, 2 males and 1 female, the mean age : 77). In 7 of 9 cases, who were given pregabalin before prescribing makyoyokukanto plus, makyoyokukanto plus was more effective than pregabalin. Furthermore, we have continued to observe 10 cases for over a year. Two of 10 cases were completely cured even if makyoyokukanto plus was discontinued. In 5 cases we switched from makyoyokukanto plus to yokuininto extracts combined with powdered cinnamon bark and processed aconite root, which was comparable to makyoyokukanto plus in its effect. Makyoyokukanto or yokuininto extracts combined with powdered cinnamon bark and processed aconite root were effective for chronic sciatica.

Dual actions on gout flare and acute kidney injury along with enhanced renal transporter activities by Yokuininto, a Kampo medicine.

BACKGROUND: Prolonged hyperuricemia is associated with kidney disease or gouty arthritis. Whether Yokuininto, a commercially available Kampo medicine that has been used for osteoarthritis or rheumatoid arthritis, can exhibit anti-hyperuricemic and inflammatory effects remains elusive. In the present study, Yokuininto exerts multiple homeostatic action on serum uric acid (sUA) levels by blocking pro-inflammatory cytokine activities and inducing uricosuric function with anti-renal injury functions. METHODS: The sUA was measured in potassium oxonate (PO)-administered mice. Renal transporter uptake assays were performed using HEK293 cells overexpressing OAT1, OCT2 or OAT3, MDCKII cells overexpressing BCRP, and Xenopus oocytes overexpressing OAT3 or URAT1. Immunoblot and ELISA assays were performed to detect the molecules (OAT3, GLUT9, XO, NGAL, KIM-1 and IL-1α) in various human kidney cell lines. Cell viability analysis was performed to evaluate the cytotoxicity of Yokuininto [Ephedrine + pseudoephedrine 21.94%; Paeoniflorin 35.40% and Liquiritin 16.21% relatively measured by the ratios (HR-MS2 intensity / HR-MS1 intensity)]. RESULTS: Yokuininto (300 mg/kg) significantly reduced sUA by approximately 44% compared to that of PO-induced mice. The OAT3 levels were decreased in PO-induced hyperuricemic condition, whereas the GLUT9 transporter levels were markedly increased. However, PO did not alter the levels of URAT1. Yokuininto significantly inhibited the lipopolysaccharide (LPS)-induced secretion of IL-1α by approximately 63.2% compared to the LPS-treated macrophages. In addition, Yokuininto inhibited nitric oxide synthesis by approximately 33.7 (500 µg/mL) and 64.6% (1000 µg/mL), compared to that of LPS-treated macrophages. Yokuininto markedly increased xanthine oxidase inhibition activity. Furthermore, interleukin-1α (IL-1α), a pro-inflammatory cytokine, elevated neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) activities in LLC-PK1 cells. Expression of renal inflammatory biomarkers, NGAL and KIM-1, was reduced under the Yokuininto treatment by 36.9 and 72.1%, respectively. CONCLUSIONS: Those results suggest that Yokuininto may suppress inflammation and protect against kidney dysfunction in hyperuricemia. The present findings demonstrated that Yokuininto lowered sUA through both increased uric acid excretion and decreased uric acid production. Our results may provide a basis for the protection of prolonged hyperuricemia-associated kidney injury with uric acid-lowering agents such as Yokuininto.

A Case of Rheumatic Arthritis Successfully Treated by Boiogito and Yokuininto with Bushi / 日本東洋医学雑誌

Here I report a case of chronic rheumatic arthritis, which was successfully treated with boiogito, yokuininto and bushi, leading to complete remission. A 38 year-old woman, null gravida, has been suffering from strong pain and frequent sense of numb in both hand joints. Previous orthopedic specialist diagnosed as rheumatic arthritis. Since she had a hope of getting pregnant, she came to our outpatient clinic, seeking Kampo treatment. Clinical examination revealed a positive test of anti-CCP antibody (>200) or rheumatoid factor as 32.4. Kampo treatment was started with keishikajutsubuto besides bushi, or eppikajutsuto with bushi, which were not effective sufficiently. Finally, combined agents with yokuininto and boiogito dramatically reduced pain, visual analogue scale score or CRP level, and relieved pain in bilateral hand joints, leading to complete remission. Yokuininto is applied to the cases with pains, chilliness or sense of numb in limb joints or muscles. Furthermore, boiogito is administered to the patients with edematous, painful and/or swollen joints. Both agents contain several herbal medicines with pain relieving spasmolytics, redistributing of tissue fluid or anti-inflammatory actions. From these findings, agents used in this case appear to work towards redistributing tissue fluid, easing local immune reaction or relieving pains powerfully. It is thought that combined agents with boiogito and yokuininto could be a reliable option for the treatment of rheumatic arthritis.

The Consideration of the Patients with Rheumatoid Arthritis Successfully Treated with Yokuinin-to-kami / 日本東洋医学雑誌

We report on three RA patients successfully treated with Yokuinin-to-ka-kyokatsu-dokkatsu-bofu (Yokuinin-to-kami). The first patient was a 47-year-old woman. In 1983, she visited a nearby hospital due to bilateral wrist joint pain. Her condition was diagnosed as RA. She was treated with gold sodium thiomalate (GST) and non-steroidal anti-inflammatory drugs (NSAIDs), but her symptoms did not improve. She visited our department in 1989. She was treated with Keishi-ka-ryojutsubu-to, Bushi-to which resulted in decreased arthralgia. However, in September 1995, her condition worsened. Administration of Yokuinin-to-kami improved her symptoms as well as her laboratory data after three months of treatment. The second patient was a 50-year-old woman. In 1986, she visited a nearby hospital with bilateral wrist joint pain. Several Kampo formulas were subsequently administered at a pharmacy. In 1991, she visited our hospital and her condition improved after treatment with Keishi-ka-ryojutsu-to-ka-boi-ogi-yokuinin. However, in May 1996, she complained of severe pain and swelling at the right shoulder joint. Treatment with Yokuinin-to-kami improved her symptoms, as well as decreased serum C-reactive protein (CRP). The third case involved a 42-year-old woman who exhibited polyarthralgia in June 1991. She visited a neighborhood hospital and was diagnosed as having RA. She was treated with NSAIDs and bucillamine. She first visited our hospital in1993. We treated her with Keishi-ni-eppi-itto-ka-ryojutsubu and Keishi-shakuyaku-timo-to, but the polyarthralgia worsened in May 1996. Subsequently, we treated her with Yokuinin-to-kami which resulted in improvement symptoms, as well as decreased serum CRP.<br>To identify the target group for Yokuinin-to-kami, we further analyzed the characteristics of the patients successfully treated with this formula. Yokuinin-to-kami was administered to nine patients with RA, and the symptoms in five patients improved, but the remaining patients did not respond. The score of stasis of body fluids and deficiency of blood was not considerably different between the two groups. Interestingly, there was a difference in the variation of joint symptoms throughout the day. Namely, the successfully treated patients complained of joint symptom in the evening more than in the morning. These observations suggest that Yokuinin-to-kami is a useful agent for the treatment of a subset of patients with RA, and that joint pain in the evening might be an indicator for this treatment.

The Effect of Kampo Medicine in Rats with Adjuvant Arthritis; The Effect of Sokei-kakketsu-to and Yokuinin-to on Serum Dipeptidyl Aminopeptidase IV / 日本東洋医学雑誌

Rats with adjuvant arthritis (AA rats) show obvious inhibition of the local inflammation when steroids (DXM) are administered. But the contraction of thymic or adrenal atrophy, spleen hypertrophy, and reduction of activity of serum dipeptidyl aminopeptidase IV are recognized. In rats where Sokei-kakketsu-to or Yokuinin-to was administered, prominent anti-inflammatory effects like dexamethasone were not found; however the contraction of thymic or adrenal atrophy, spleen hypertrophy, and reduction of activity of serum dipeptidyl aminopeptidase IV was not recognized. In addition, after withdrawal of drugs, rebound in regional joints did not occurr as with steroids, and the reducing effect for arthrocele was prolonged. Therefore, it was concluded that those two formulations have an effect on the immune system —with anti-inflammatory effects for AA rats— and these action mechanisms are different from that of steroids (DXM).

Hematological Change in the Adjuvant-Induced Arthritis of Rats (II). Effects of Kampo Medicine Extracts on the Inflammatory Index Substances and Platelet / 日本東洋医学雑誌

The hematological effects of Sokeikakketsu-to, Yokuinin-to, Keisi-ka-jutsubsu-to, Eppi-ka-jutsu-to, and Sairei-to observed on the AA rats were investigated. The time course of blood count and albumin, sialic acid and acid-soluble glycoprotein in the serum whs. were measured. Sokeikakketsu-to had the strongest anti-inflammatory effect on the improvement of Inflammatory Index Substances, platelets, and the Arthritis Score for changes in synovitis. Yokuinin-to was also effective. When these Kampo medicines were administered in the early stages of AA, Sokeikakketsu-to improved the AA signficantly. The results may suggest that Sokeikakketsu-to works for the control of autoimmunity. On the other hand, Keisi-ka-jutsubu-to aggravated the AA when it was administered in the early stages of the AA.

Effects of Kampo Medicine Extracts on the Arthritis Score and Histological Change of Synovitis in Adjuvant-Induced Arthritis in Rats. (I) / 日本東洋医学雑誌

The effects of Sokei-kakketsu-to, Yokuinin-to, Keisi-ka-zyutsubu-to, Eppi-ka-jutsu-to, and Saireito extracts on Adjuvant-induced arthritis (AA) in rats were investigated. After administering AA, we measured the volume of rat hindpaw as the inflammation index, and observed the changes of synovitis histologically. Each extract showed different effects on AA rats. Yokuinin-to and Sokei-kakketsu-to had remarkable effects on inflammation and changed the histological observations of synovitis. Eppi-ka-jutsu-to also had effects on the uninjected hindpaw, but Keisi-ka-jutsubu-to and Sairei-to had no effect on hindpaw inflammation, nor did they change synovitis histologically.

Treatment of Arthralgia in Psoriatic Arthritis with Yokuinin-to / 日本東洋医学雑誌

Oral administration of Yokuinin-to was added to the previous drugs in 4 patients with psoriatic arthritis. All of the cases responded to the therapy without adverse effects. In 3 of 4 cases, the previous drugs, i. e, corticosteroids, etretinate, or non-steroidal anti-inflammatory drugs (NSAIDs), were able to be discontinued after the beginning of the Yokuinin-to therapy. The remainder had favorable control of arthralgia with Yokuinin-to alone. During the course of the therapy, there were no considerable changes in skin eruption in all 4 cases. We consider Yokuinin-to one of the first drugs of choice in the treatment of arthralgia in patients with psoriatic arthritis.