Kampo Formula Research Articles

Inhibitory Effect of Kampo (Japanese Traditional Herbal Medicine) Therapy on the Development of Hepatocellular Carcinoma in Patients with HCV-related Chronic Hepatic Disease-Usefulness of Kampo Therapy based on Traditional Theory-

We evaluated the effect of Kampo therapy in which Kampo formulae were selected based on Japanese traditional theory, on the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related chronic liver disease. One hundred forty HCV-infected outpatients without HCC at their first examination and who were observed for more than one year, were included. The patients were divided into three groups according to the initial platelet count (Plt): Plt less than 10×104/μL (Group I), Plt between 10×104/μL and 14×104/μL (Group II), and Pit greater than 14×104/μL (Group III). For each patient, Kampo formulae were selected according to the patient's symptoms and physical findings at each clinic visit. The incidence of HCC calculated by the person-years method, was 0.89% in Group I. 1.55% in Group II and 0.29% in Group III. The annual incidence of HCC among our patients was low compared with that among untreated patients in previous reports. In addition, the incidence of HCC among our patients was low compared with that of previous studies where Shosaikoto or Juzentaihoto was administered for a long period of time. In the present study, age over 60 years was a possible risk factor for HCC. However, sex and patterns of the change in alanine aminotransferase level (ALT) were not associated with the development of HCC. A total of 53 different Kampo formulae were prescribed, for all patients, with Hochuekkito being the most frequent. These results suggest that Kampo treatment in which Kampo formulae are selected based on traditional theory, may be more useful than treatment by a single Kampo formula for preventing the development of HCC in patients with HCV-related chronic liver disease.

An Alternative Approach to Atopic Dermatitis: Part I-Case-Series Presentation.

Atopic dermatitis (AD) is a complex disease of obscure pathogenesis. A substantial portion of AD patients treated with conventional therapy become intractable after several cycles of recurrence. Over the last 20 years we have developed an alternative approach to treat many of these patients by diet and Kampo herbal medicine. However, as our approach is highly individualized and the Kampo formulae sometimes complicated, it is not easy to provide evidence to establish usefulness of this approach. In this Review, to demonstrate the effectiveness of the method of individualized Kampo therapy, results are presented for a series of patients who had failed with conventional therapy but were treated afterwards in our institution. Based on these data, we contend that there exist a definite subgroup of AD patients in whom conventional therapy fails, but the ‘Diet and Kampo’ approach succeeds, to heal. Therefore, this approach should be considered seriously as a second-line treatment for AD patients. In the Discussion, we review the evidential status of the current conventional strategies for AD treatment in general, and then specifically discuss the possibility of integrating Kampo regimens into it, taking our case-series presented here as evidential basis. We emphasize that Kampo therapy for AD is more ‘art’ than technology, for which expertise is an essential pre-requisite.

Clinical Efficacy of EH0202, a Kampo Formula, on the Health of Middle-Aged Women

To investigate the clinical effects of EH0202, a Japanese herbal supplement, on the menopausal symptoms and physical status of peri- and post-menopausal women. Thirty-two post-menopausal women (53.0+/-5.1 years) presented with menopausal complaints were enrolled in the clinical study. Patients were administered an herbal supplement, EH0202 (6 g/day for 6 months), and were assessed for improvement of their overall symptoms using the Greene Climacteric Scale and the Visual Analog Scale (VAS). Blood pressure, skin surface blood flow and plasma lipid profiles were measured before and 1,3 and 6 months after EH0202 administration. There was a significant decrease in the climacteric scale score (P < 0.001) and VAS (P < 0.0001) after 6 months of EH0202 treatment. There was a significant decrease in systolic (P < 0.001) and diastolic (P < 0.05) blood pressure, and a significant decrease in facial skin surface blood flow (P < 0.05) after 3 months of EH0202 administration. We observed a significant decrease in plasma TG and LDL-cholesterol concentrations after 3 months of EH0202 administration (P < 0.05). EH0202 (MACH) reduced blood pressure, excess facial skin blood flow (flushing) and abnormal lipid levels, as well as clinically improved menopausal symptoms in post-menopausal women. In post-menopausal women, this product appears to help maintain normal biological function and improves quality of life.

Repair of amyloid β(25–35)-induced memory impairment and synaptic loss by a Kampo formula, Zokumei-to

Although Zokumei-to (ZMT), a Kampo formula, has been used for postapopletic sequelae such as paralysis and logopathy, only few studies of this drug have been carried out. We hypothesized that ZMT may affect neuronal plasticity and investigated whether or not this drug is capable of improving learning impairment and synaptic loss observed in patients with Alzheimer's disease (AD). Amyloid β(25–35) [Aβ(25–35)] (4.7 nmol) was intracerebroventricularly injected into ddY mice (male, 6 weeks old). Fourteen days after the injection, mice were given ZMT extract (500 mg/kg/day) per os for 15 days. In a memory acquisition test, the Aβ(25–35)-injected mice required more time to master this task than did mice in the saline- or reverse peptide Aβ(35–25)-treated groups. ZMT-treated mice shortened escape latencies during trial days 3–5, but not significantly. Three days after the last drug treatment, a retention test was performed. Following ZMT, the number of crossings over a platform was significantly decreased in Aβ(25–35)-injected mice compared with those in the control groups. However, ZMT-treated mice showed complete recovery of this number. Although Aβ(25–35) injection decreased synaptophysin expression in the cerebral cortex and the hippocampus, ZMT treatment significantly increased the level of expression of synaptophysin up to the control level. Donepezil hydrochloride (DNP, 0.5 mg/kg/day, po) clinically used for AD had no effect on memory retention and synaptophysin levels. Aβ(25–35)-induced neuronal loss was not observed in any region of the brain. The present results suggest that memory impairment and synaptic loss in AD patients may be improved by treatment with ZMT, even after such impairment has already progressed.

In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomes.

Although it is well known that drug-drug interactions may lead to toxicity and therapeutic failure, little is known about the incidence and consequences of herb-drug interactions in patients receiving Kampo medicines. We evaluated the frequency of the combined use of Kampo medicines and Western drugs at Osaka University Hospital, and investigated the effects of these formulae on the metabolic activity of different cytochrome P450 (CYP) isoforms using pooled microsomes obtained from human liver. Twenty-two Kampo formulae were used together with 40 Western drugs catalyzed by the CYP isoforms CYP3A4, CYP2C9, CYP2D6 and CYP1A2. Among the Kampo medicines, HOCHUEKKI-TO, SHOSAIKO-TO, NINJINYOUEI-TO, SAIREI-TO and KAKKON-TO were most frequently used during the study period (1996-2000). These were co-administered with 11 categories of drugs, which are substrates for CYP3A4. HOCHUEKKI-TO and SAIREI-TO were competitive inhibitors of CYP3A4 with Ki values of 0.65 and 0.1 mg/mL, respectively. HOCHUEKKI-TO, SHOSAIKO-TO and SAIREI-TO inhibited the metabolic activities of CYP2C9, but had no effect on CYP2D6. HOCHUEKKI-TO and SAIREI-TO exhibited non-competitive inhibition of the metabolic activity of CYP2C9 with a similar Ki value (0.7-0.8 mg/mL). SAIRE-TO (0.25 mg/mL) was a potent inhibitor of CYP1A2 (inhibition > 68%). Frequently used Kampo medicines may interact with Western drugs, which are substrates for CYP3A4, CYP2C9 and CYP1A2. Their co-administration should be undertaken with care.

Herbal Medicine and False-Positive Results on Lymphocyte Transformation Test

In vitro mitogenic activity of 16 herbs and 3 Kampo (herbal medicine) formulae have been reported in experimental studies. It is not known how many herbs and Kampo formulae in total have mitogenic activity. Lymphocyte transformation test (LTT) is generally utilized to diagnose drug-induced liver injury. In LTT, mitogenic activity is assessed by measuring 3H-thymidine incorporation. The objective of the present study was to determine which herbs and which Kampo formulae caused false-positivity on LTT. We examined 2496 summaries of all admission records from 1979 to 1999 in our department. We selected patients in whom liver injuries were diagnosed as definitely unrelated to Kampo medication. In these patients, LTT was performed for some herbs contained in the suspect Kampo medicines, resulting in positive LTT for 17 herbs: Evodiae Fructus (Goshuyu), Zizyphi Fructus (Taiso), Ginseng Radix (Ninjin), Zingiberis Rhizoma (Shokyo), Hoelen (Bukuryo), Aconiti Tuber (Bushi), Angelicae Radix (Toki), Cnidii Rhizoma (Senkyu), Rehmanniae Radix (Jio), Ephedrae Herba (Mao), Anemarrhenae Rhizoma (Chimo), Cinnamomi Cortex (Keihi), Bupleuri Radix (Saiko), Artemisiae Capillari Spica (Inchinko), Persicae Semen (Tonin), Moutan Cortex (Botanpi) and Paeoniae Radix (Shakuyaku). These results were considered false-positive, because the results were observed in the "definitely unrelated" patients. Mitogenic activity inherent to some herbs and Kampo formulae may sometimes cause false-positivity on LTT in clinical situations. These examples suggest that LTT for Kampo formulae may be unreliable as a diagnostic method for drug-induced liver injury.

The combination therapy of Ephedra herb and Loxoprofen caused gastric lesions in mice.

The combination therapy of a Kampo formula and an analgesic-antipyretic agent is often used for the common cold in Japan. We investigated the effect of such a combination therapy, using the Ephedra herb, which is a common ingredient of Kakkon-to and Mao-to, and Loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), on fever induced in an experimental model of mice under strong stress. The combination therapy of Ephedra herb and Loxoprofen caused gastric mucosal lesions and loss of body weight. It is considered that this combination therapy should be avoided because of its adverse effects.

Effects of hokoei-to (pugongying-tang), a Kampo formula, on monoamine content in brain regions and mitogenic activity of splenic lymphocytes in ovariectomized mice.

Hokoei-to (pugongying-tang) is one of the Kampo formulae clinically used for gynecological disturbances such as lack of lactation and mammary swelling. We investigated the effect of hokoei-to on the nervous and immune systems in ovariectomized mice as a climacteric disorder model. Hokoei-to suppressed the decrease of monoamines in the ventral hippocampus and dorsal hippocampus of ovariectomized mice. It was shown that the hokoei-to could improve the metabolic turnover of dopamine. The mitogenic activity of lymphocytes in the spleen was reduced after ovariectomy; a suppression of this reduced activity was observed in the group given hokoei-to.

Effect of mirabilitum in formularization: change of prolyl endopeptidase inhibitory activity and of constituents using the preparation method of Tokaku-joki-to.

To clarify the effect of Mirabilitum in formularization, change of prolyl endopeptidase inhibitory activity and of constituents using the preparation method of a Kampo formula Tokaku-joki-to ([Japanese characters: see text], Persia and Rhubarb combination) was examined by the liquid chromatography-mass spectroscopy (LC-MS) method. Mirabilitum under boiling condition caused qualitative and quantitative change of the constituents through hydrolysis which caused a change of its activity. This was considered to be the main reason the classical Chinese medical book "Shang han lun ([Japanese characters: see text])" specified that Mirabilitum should be added at a later stage of decoction.

Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice.

Perilla frutescens Britton (perilla, Labiatae) is a medicinal herb prescribed in Saiboku-to [Japanese letters: see text], which is a Kampo formula effective for allergic diseases such as bronchial asthma. The present study was conducted to evaluate the anti-allergic effect of orally administered perilla decoction and to identify the active constituents using mice ear-passive cutaneous anaphylaxis (PCA)-reaction, which is one of the animal models for type I allergy. Perilla decoction significantly suppressed PCA-reaction, and the inhibition % at the dose of 500 mg/kg was 43%. The perilla decoction contains 5.3% of luteolin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide], 1.6% of apigenin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide], 0.49% of scutellarin, and 2.5% of rosmarinic acid (weight of compound/dried weight of perilla decoction %), respectively. When these constituents were orally administered to mice at the dose equivalent to 500 mg/kg of perilla decoction, rosmarinic acid and apigenin 7-O-[beta-glucuronosyl(2-->1)beta-glucuronide] significantly suppressed PCA-reaction, and their inhibition % was 41% (p<0.01) and 32% (p<0.05), respectively. Since the inhibition % or perilla decoction and rosmarinic acid were nearly equal, the anti-allergic effect of perilla decoction depends primarily on rosmarinic acid. The standard Saiboku-to decoction contained 0.013% of rosmarinic acid, which was too low to exhibit anti-allergic activity in a daily dose of Saiboku-to in adults, suggesting that perilla would be prescribed in Saiboku-to to exhibit other pharmacological effects than its anti-allergic activity, such as a sedative.

Prolyl Endopeptidase Inhibitory Activity of Fourteen Kampo Formulas and Inhibitory Constituents of Tokaku-joki-to.

Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme playing a role in the metabolism of proline-containing neuropeptides which have been suggested to be involved in learning and memory processes. In screening for PEP inhibitors from fourteen traditional Kampo formulas, we found that Tokaku-joki-to shows a significant inhibitory activity. Examination of the constituents of the Kampo formula resulted in the isolation of two new compounds, cis-3,5,4'-trihydroxystilbene 4'-O-beta-D-(6-O-galloyl)glucopyranoside (10) and 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-(6-O-galloyl-2-O-cinnamoyl)glucopyranoside (16), along with twenty-five known compounds, cinnamic acid (1), protocatechuic acid (2), gallic acid (3), torachrysone 8-O-beta-D-glucoside (4), emodin (5), emodin 8-O-beta-D-glucoside (6), 3,5,4'-trihydroxystilbene 4'-O-beta-D-glucopyranoside (7), 3,5,4'-trihydroxystilbene 4'-O-beta-D-(2-O-galloyl)glucopyranoside (8), 3,5,4'-trihydroxystilbene 4'-O-beta-D-(6-O-galloyl)glucopyranoside (9), 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-glucopyranoside (11), isolindleyin (12), lindleyin (13), 4(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-(2,6-di-O-galloyl)glucopyranoside (14), 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D-(2-O-galloyl-6-O-cinnamoyl)glucopyranoside (15), 1-O-galloylglucose (17), 1,2,6-tri-O-galloylglucose (18), gallic acid 4-O-beta-D-(6-O-galloyl)glucopyranoside (19), liquiritigenin (20), liquiritigenin 4'-O-beta-D-glucoside (21), liquiritigenin 7,4'-diglucoside (22), liquiritigenin 4'-O-beta-D-apiofuranosyl-(1-->2)-beta-D-glucopyranoside (23), licuroside (24), (-)-epicatechin (25), (-)-epicatechin 3-O-gallate (26) and (+)-catechin (27). Among these compounds, twelve (7-10, 14-16, 18, 19, 24-26) showed noncompetitive inhibition with an IC50 of 22.9, 3.0, 14.9, 2.8, 10.5, 0.69, 8.2, 0.44, 9.39, 26.5, 28.1 and 0.052 microM, respectively.

The effect of kampo formulae on bone resorption in vitro and in vivo. II. Detailed study of berberine.

We previously isolated berberine from aqueous extracts of tsu-kan-gan, a Kampo formula used for the treatment of osteoporosis. Berberine caused an inhibitory effect on parathyroid hormone (PTH)-stimulated bone resorption in neonatal mouse bone. In this report we describe the inhibitory effect of berberine on the formation of osteoclast-like multinucleated cells (OCLs) in the co-culture of mouse osteoblastic cells and bone marrow cells in the presence of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], PTH and interleukin-1alpha (IL-1alpha). Berberine dose-dependently inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive OCLs induced by 1alpha25(OH)2D3, PTH and IL-1alpha. We prepared OCLs in the co-culture of osteoblastic cells and bone marrow cells. The effect of berberine on pit formation by OCLs was examined using dentin slices. As OCLs are terminally differentiated multinucleated cells, the survival of OCLs affects the bone-resorbing activity of OCLs. This prompted us to count the number of TRAP-positive OCLs on the slices. Berberine dose-dependently inhibited pit formation and caused a decrease in the number of TRAP-positive OCLs. Calcitonin (CT) inhibited pit formation without affecting the number of OCLs. Berberine accelerated the cell death in OCLs cultivated on a culture plate, but CT did not affect the cell death of OCLs. This suggests that the decrease in the number of OCLs on dentin slices may be due to apoptotic cell death in OCLs. In fact, Hoechst 33258 staining revealed that the treatment of OCLs with berberine resulted in condensed nuclei and a decrease in cell size. Oral administration of the berberine (30 and 50 mg/kg/d) to ovariectomized rats prevented a decrease in bone mineral density (BMD) of the lumbar vertebra without affecting the weight of the uterus and plasma concentration of estradiol. These results suggested that berberine prevented a decrease in BMD in vivo by inhibiting osteoclastic bone resorption.

The effect of Kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan.

Four water extracts of Kampo formulae (Yi-kkan-sen, Dai-ho-in-gan, Ni-chi-gan, Tsu-kan-gan) were screened for their inhibitory activities on bone resorption induced by parathyroid hormone (PTH) in organ culture using neonatal mouse parietal bones. Among the Kampo formulae, Tsu-kan-gan (TKG) showed the most potent inhibitory activity. We further fractionated the TKG water extract by monitoring the inhibitory activity on bone resorption stimulated by PTH in vitro. The MeOH fraction of the water extract inhibited PTH-stimulated bone resorption, and its inhibitory activity was more potent than those of other fractions. The MeOH fraction was then subjected to Sephadex LH-20 column chromatography to give fractions I, II and III, which were examined for bone resorption activity. Fraction I inhibited PTH-stimulated bone resorption, and its inhibitory activity was more potent than those of the other fractions. Upon oral administration of the three fractions (100 mg/kg/d) to ovariectomized (OVX) mice, fractions I and III prevented the decrease of bone mineral density (BMD) of the lumbar vertebra. Eleven compounds isolated from the MeOH fraction were examined for their inhibitory effect on PTH-stimulated bone resorption. Among them, berberine (1), syringin (3), limonin (4) and mangiferin (10) showed a significant inhibitory effect on bone resorption. In the formation assay of osteoclast-like cells, these compounds decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). The inhibitory effect of TKG on bone resorption may be at least partly due to the inhibitory action of these compounds.

Synergistic effects of inchin‐ko‐to (Yin‐Chen‐Hao‐Tang) and ursodeoxycholic acid on cholestasis caused by α‐naphthyl isothiocyanate

AbstractThe effects of the combination of Inchin‐ko‐to, a kampo formulation, and ursodeoxycholic acid on experimental cholestasis were investigated. When administered intraduodenally at noneffective doses of these drugs to rats with intrahepatic cholestasis caused by α‐naphthyl isothiocyanate, the bile flow returned to a near‐normal level and the serum bile acid profile was improved. Among the major components of the kampo formula, Artemisiae capillaris Flos contributed to the change in the bile flow, and Gardeniae Fructus contributed to the improved serum bile acid profile, because ursodeoxycholic acid increased and cholic acid decreased. The results show that urosdeoxycholic acid and Inchin‐ko‐to synergistically improved experimental cholestasis and that this effect occurred because of different functions of the components of Inchin‐ko‐to.

Efficacy of Kakkon‐to, a traditional herb medicine, in herpes simplex virus type 1 infection in mice

Kakkon-to is one of the representative traditional herb medicines (Kampo formulae) and has been used historically for the treatment of infectious diseases in China and Japan. The efficacy of this preparation was characterised using a cutaneous herpes simplex virus type 1 (HSV-1) infection in mice as a model for human viral infection. Kakkon-to at a dose corresponding to human use reduced significantly the mortality of HSV-1-infected mice and localised skin lesions. Delayed type hypersensitivity (DTH) response to HSV-1 antigen was significantly stronger in treated mice than in untreated mice. However, no histopathological difference was noted in the skin lesions between treated and untreated mice except for the size of the lesions. Kakkon-to did not inhibit the growth of HSV-1 in vitro. Natural killer cell activity, natural cytotoxic killer cell activity, and the population of T-cell subsets in spleen cells of infected mice were not affected by the drug. Kakkon-to did not augment interferon induction and anti-HSV-1 antibody production, nor increased cytokine levels such as interleukin-1 alpha, interleukin-2, interferon-gamma, and tumour necrosis factor-alpha in sera of infected mice. Thus, Kakkon-to induced strong DTH to HSV-1 in infected mice, which may have caused localisation of skin lesions and reduction in the mortality of treated mice.

漢方製剤製品情報データベースと生薬情報データベース

We have developed a combined Kampo medicine information database system. The database system comprises contains Kampo medicine products information database and a crude drugs information database. In the former, information on component crude drugs and their contents and safety is unified in a relational database for each product and compared with each other within a given Kampo formula by display scrolling. In the latter, information on application, indications, constituents, dosage and other data, is separately obtained for each crude drugs.

The Successful Treatment of a Case of Anorexia Nervosa with Anchu-san.

We present here an interesting case of anorexia nervosa that was well controlled by Ancyu-san, a traditional Japanese herbal medicine. A 17-year-old student was re-admitted to our department in December of 1990, because of anorexia and eating disorders. She had lost approximately 12kg body weight during 3 months. She was 154cm tall and weighed 26kg. Her blood pressure was 75/40mmHg, her pulse rate was 30beats/min, and her body temparature was 34.4°C. She was extremely emaciated and hyperactive. On oriental examination, a shallow complexion, a cold feeling in the limbs, postprandial headaches, and a feeling of obstruction of the external ear. Her pulse was slow and feeble. Abdominal examination revealed that the abdominal strength was reduced to 2/5 with Inai-teisui (abdominal water and gas retention). Based on these findings, this case was diagnosed as Deficient Spleen and Stomach due to Deficient Ki and Blood combined with Stagnated Ki, and therefore a candidate for the Kampo formula Ancyu-san. The patient began medication in January 1991. Her appetite improved gradually and her body weight increased from 26kg to 47kg in two months.

加味しょう遥散，及び四物湯合方の出典

加味しょう遥散，及び四物湯合方の出典

Antihypertensive Property and Renal Protection by Shichimotsu-koka-to Extract in Salt-induced Hypertension in Dahl Strain Rats

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsukoka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Effects of Kampo medicines on the clearance of circulating immune complexes in mice

Toki-Shakuyaku-san (TSS), a Japanese (Kampo) formulation which consists of six herbs, was administered orally to MRL Mp-lpr/lpr mice for 6 weeks. Clearance was measured by in vivo enzymatic immune complex clearance (EIC) assay. Glucose oxidase-anti-glucose-oxidase complexes (GAG), as a model of immune complexes (ICs), was injected into mouse tail veins and at intervals thereafter the enzyme activity of the GAG remaining in the circulation were estimated. The half life ( T 1 2 ) of GAG from the circulation was significantly shortened in the TSS-treated group. Furthermore, the amount of circulating immune complexes, measured by anti-mouse C3 ELISA, tended to decrease in the TSS-treated group. We also evaluated three other Kampo formulas, but no significant effect was observed for these formulations. We then examined the activity of the individual herbs in TSS and in formulations excluding one component herb. No significant changes were observed with individual herbs. On the other hand, the activity observed in the TSS-treated group disappeared in the TSS minus Angelicae Radix formulation and the TSS minus Atractylodis Lanceae Rhizoma formulation. These observations indicate that TSS is a potent formula and its enhancing activity on ICs clearance is strengthened by both Angelicae Radix and Atractylodis Lanceae Rhizoma.