The rhizomes of many Atractylodes species, including Atractylodes chinensis Koidzumi, Atractylodes macrocephala Koidzumi, and Atractylodes japonica Koidzumi, are collectively termed Atractylodis Rhizoma. We prepared n-hexane extracts of the three species and evaluated their anti-inflammatory effects on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among all n-hexane extracts, those of A. japonica most strongly inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 cells; five sesquiterpenes, atractylon, atractylenolide I, atractylenolide II, atractylenolide III, and 8-epiasterolid, were isolated from A. japonica. The phytochemical content of A. japonica was similar to those of A. chinensis and A. macrocephala. Moreover, the atractylon concentration was higher in A. japonica than in A. chinensis and A. macrocephala. Atractylon significantly inhibited NO and prostaglandin E2 production as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-induced RAW 264.7 cells. Atractylon (40 mg/kg) also significantly reduced the acetic-acid-induced writhing response, carrageenan-induced paw edema, and hot-plate latent pain response in mice. According to the results, A. japonica has anti-inflammatory and antinociceptive effects and atractylon is the major active component of A. japonica. Therefore, atractylon can be used as a bioactivity marker in A. japonica.

Dried citrus peels (Chimpi) is one of the most common natural medicines with qi (energy flow) rectifying and shi (dampness) drying actions, which originates from Citrus unshiu, and/or C. reticulata according to the definition of the pharmacopoeiae of Japan and China. In this study, the pharmacological effects of their extracts and major chemical constituents hesperidin and its aglycone hesperetin on anxiety were examined with an anxiety model of elevated open-platform test using ICR male mice (6-week-old) and total duration of freezing was decreased in fluoxetine-treated mice, which is a simple and highly sensitive to the effects of serotonergic anxiolytics. Moreover, yokukansankachimpihange (YKH), a combination of yokukansan with Chimpi and Hange (Pinellia) was also examined because Chimpi is considered to play a crucial part in this formula against anxious symptoms in dementia patients. The results showed that Chimpi and YKH possess a significant anxiolytic-like effect similar to that of fluoxetine, suggesting that they might be similar to fluoxetine in their pharmacological actions through the serotonergic neurotransmission pathway. Moreover, it also suggested that the major chemical constituent, hesperidin could be an active principle attributed to the antianxiety-like effects with a direct and indirect role via its aglycone hesperetin.

Background: Diarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID. Method: HLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co-and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model. Results: HLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu-and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pretreatment induced presentation of CD44-postive cells in the intestine of chemotherapytreated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.

The EtOAc-soluble portion of the 80 % (v/v) EtOH extract from the twigs of Garcinia esculenta exhibited strong xanthine oxidase inhibition in vitro. Bioassay-guided purification led to the isolation of 1,3,6,7-tetrahydroxyxanthone (3) and griffipavixanthone (8) as the main xanthine oxidase inhibitors, along with six additional compounds (1, 2, 4-7), including two new compounds (1 and 2). This enzyme inhibition was dose dependent with an IC50 value of approximately 1.2 µM for 3 and 6.3 µM for 8. The inhibitory activity of 3 was stronger than the control allopurinol (IC50 value: 5.3 µM). To our knowledge, compound 8 is the first bixanthone that demonstrated potent XO inhibitory activity in vitro. The structures of the new compounds were established by spectroscopic analysis, and the optical properties and absolute stereochemistry of racemic (±) esculentin A (2) were further determined by the calculation of the DP4 probability and analysis of its MTPA ester derivatives.

Abstract:Hallucinations are a common non-motor symptom of Parkinson's disease and various forms of dementias. Yokukansan and Yokukansankachimpihange have attracted attention due to their effectiveness in the treatment of hallucinations of dementia. To clarify which component in these formulas contribute to the effects, at first, we focused on their differences in compositions to examine the pharmacological effects on the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head-twitch response (HTR) in mice that has been used as animal hallucination model. Results indicated that water extract of Byaku-jutsu (Atractylodes japonica) showed a stronger inhibitory effect on DOI-induced HTR than that of So-jutsu (A. lancea) corresponding to their major constituents of atractylenolide III and β-eudesmol, and suggested that the major constituents should be active constituents contributing to the antihallucination effects of Byaku-and So-jutsu. Besides, the part B-C ring (butenolide) in atractylenolide III was found to be similar to the structure of serotonin and suggested that the B-C ring may partially play role in antagonistic activity against serotonin receptors. Thus, a novel, rational design of butenolide-related compounds may as potential lead compounds for new drug development. Analysis of the chemical components of Byaku-and So-jutsu and further study on their structure-activity relationships are currently in progress.