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Ulcerative colitis (UC) is a chronic inflammatory disease of the intestines that can significantly impact quality of life and lead to various complications. Currently, 5-aminosalicylic acid derivatives, corticosteroids, immunosuppressants, and biologics are the major treatment strategies for UC, but their limitations have raised concerns. Atractylenolides (ATs), sesquiterpene metabolites found in Atractylodes macrocephala Koidz., have shown promising effects in treating UC by exerting immune barrier modulation, alleviating oxidative stress, gut microbiota regulation, improving mitochondrial dysfunction and repairing the intestinal barrier. Furthermore, ATs have been shown to possess remarkable antifibrosis, anti-thrombus, anti-angiogenesis and anti-cancer. These findings suggest that ATs hold important potential in treating UC and its complications. Therefore, this review systematically summarizes the efficacy and potential mechanisms of ATs in treating UC and its complications, providing the latest insights for further research and clinical applications. [ABSTRACT FROM AUTHOR]

Atractylenolides, comprising atractylenolide I, II, and III, represent the principal bioactive constituents of Atractylodes macrocephala, a traditional Chinese medicine. These compounds exhibit a diverse array of pharmacological properties, including anti-inflammatory, anti-cancer, and organ-protective effects, underscoring their potential for future research and development. Recent investigations have demonstrated that the anti-cancer activity of the three atractylenolides can be attributed to their influence on the JAK2/STAT3 signaling pathway. Additionally, the TLR4/NF-κB, PI3K/Akt, and MAPK signaling pathways primarily mediate the anti-inflammatory effects of these compounds. Atractylenolides can protect multiple organs by modulating oxidative stress, attenuating the inflammatory response, activating anti-apoptotic signaling pathways, and inhibiting cell apoptosis. These protective effects extend to the heart, liver, lung, kidney, stomach, intestine, and nervous system. Consequently, atractylenolides may emerge as clinically relevant multi-organ protective agents in the future. Notably, the pharmacological activities of the three atractylenolides differ. Atractylenolide I and III demonstrate potent anti-inflammatory and organ-protective properties, whereas the effects of atractylenolide II are infrequently reported. This review systematically examines the literature on atractylenolides published in recent years, with a primary emphasis on their pharmacological properties, in order to inform future development and application efforts. [ABSTRACT FROM AUTHOR]

Drugs that exhibit a high degree of tumor cell selectivity while minimizing normal cell toxicity are an area of active research interest as a means of designing novel antitumor agents. The pharmacological benefits of Chinese herbal medicine-based treatments have been the focus of growing research interest in recent years. Sesquiterpenoids derived from the Atractylodes macrocephala volatile oil preparations exhibit in vitro and in vivo antitumor activity. Atracylenolides exhibit anti-proliferative, anti-metastatic, and immunomodulatory activity in a range of tumor cell lines in addition to being capable of regulating metabolic activity such that it is a promising candidate drug for the treatment of diverse cancers. The present review provides a summary of recent advances in Atractylenolide-focused antitumor research efforts.

Atractylenolides, comprising atractylenolide I, II, and III, represent the principal bioactive constituents of Atractylodes macrocephala, a traditional Chinese medicine. These compounds exhibit a diverse array of pharmacological properties, including anti-inflammatory, anti-cancer, and organ-protective effects, underscoring their potential for future research and development. Recent investigations have demonstrated that the anti-cancer activity of the three atractylenolides can be attributed to their influence on the JAK2/STAT3 signaling pathway. Additionally, the TLR4/NF-κB, PI3K/Akt, and MAPK signaling pathways primarily mediate the anti-inflammatory effects of these compounds. Atractylenolides can protect multiple organs by modulating oxidative stress, attenuating the inflammatory response, activating anti-apoptotic signaling pathways, and inhibiting cell apoptosis. These protective effects extend to the heart, liver, lung, kidney, stomach, intestine, and nervous system. Consequently, atractylenolides may emerge as clinically relevant multi-organ protective agents in the future. Notably, the pharmacological activities of the three atractylenolides differ. Atractylenolide I and III demonstrate potent anti-inflammatory and organ-protective properties, whereas the effects of atractylenolide II are infrequently reported. This review systematically examines the literature on atractylenolides published in recent years, with a primary emphasis on their pharmacological properties, in order to inform future development and application efforts.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestines that can significantly impact quality of life and lead to various complications. Currently, 5-aminosalicylic acid derivatives, corticosteroids, immunosuppressants, and biologics are the major treatment strategies for UC, but their limitations have raised concerns. Atractylenolides (ATs), sesquiterpene metabolites found in Atractylodes macrocephala Koidz., have shown promising effects in treating UC by exerting immune barrier modulation, alleviating oxidative stress, gut microbiota regulation, improving mitochondrial dysfunction and repairing the intestinal barrier. Furthermore, ATs have been shown to possess remarkable anti-fibrosis, anti-thrombus, anti-angiogenesis and anti-cancer. These findings suggest that ATs hold important potential in treating UC and its complications. Therefore, this review systematically summarizes the efficacy and potential mechanisms of ATs in treating UC and its complications, providing the latest insights for further research and clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qian, Ye, Hu, Wu, Chen, Li, Hu, Zhao, Zhang, Yang, Xudong, Ye and Qin.)

Atractylodes macrocephala Koidz is a widely used as a traditional Chinese medicine. Atractylenolides (-I, -II, and -III) are a class of lactone compounds derived from Atractylodes macrocephala Koidz. Research into atractylenolides over the past two decades has shown that atractylenolides have anti-cancer, anti-inflammatory, anti-platelet, anti-osteoporosis, and antibacterial activity; protect the nervous system; and regulate blood glucose and lipids. Because of structural differences, both atractylenolide-I and atractylenolide-II have remarkable anti-cancer activities, and atractylenolide-I and atractylenolide-III have remarkable anti-inflammatory and neuroprotective activities. We therefore recommend further clinical research on the anti-cancer, anti-inflammatory and neuroprotective effects of atractylenolides, determine their therapeutic effects, alone or in combination. To investigate their ability to regulate blood glucose and lipid, as well as their anti-platelet, anti-osteoporosis, and antibacterial activities, both in vitro and in vivo studies are necessary. Atractylenolides are rapidly absorbed but slowly metabolized; thus, solubilization studies may not be necessary. However, due to the inhibitory effects of atractylenolides on metabolic enzymes, it is necessary to pay attention to the possible side effects of combining atractylenolides with other drugs, in clinical application. In short, atractylenolides have considerable medicinal value and warrant further study. [ABSTRACT FROM AUTHOR]

The article aimed to study intestinal absorption and pharmacokinetic characterization of three atractylenolides from low polar component of Atractylodes (LPA). LC-MS method was used to find absorbed components combined with pharmacochemistry and to determine plasma concentration combined with DAS 3.0 to calculate the PK parameters. Moreover, the everted gut sac model was used to investigate rat small intestinal absorption and transport characterization of atractylenolide I, II, III. In total, eight components were identified from the absorbed components, including two lactones (6, 7), three volatile oil (2, 3, 8), acids (1), prenylated dihydrobenzofuran derivative (4) and luteolin (5), respectively. The three atractylenolides are rapidly absorbed with Tmax as 1 h and more compatible with the two-compartment model in rats, and good linearity between Cmax and concentration. The cumulative absorption per unit area Q (ug·cm−2) of three atractylenolides were no significant difference and all linearly absorbed with different time, concentration in different intestinal segments, which indicated its absorption process was passive transport. In addition, the atractylenolides III showed most high absorption rate in all intestinal segments, and the absorption site of atractylenolides II was mainly duodenum segments. LC-MS is a systematically applicable approach for rapid screening, identification and quanlitation of absorbed components derived from atractylodes in vivo. Three atractylenolides showed similar PK characterization and passive transport through all intestinal segments. It looks more safe with less drug interaction. [ABSTRACT FROM AUTHOR]

The enzymatic activities (POD, PPO, CAT, PAL), as protective enzymes in the leaves of Atractylodis maceocephalae koidz , were tested by treating different concentrations of polysaccharides isolated from Sclerotium rolfsii sacc (P. S. rolfsii ) at 0 mg/l, 20 mg/l, 200 mg/l and 400 mg/l against S. rolfsii , and atractylenolides as a phytoalexin in the rhizome of A. maceocephalae were evaluated in compared with control. It was evident that the plant under stress by pathogen has instigated the significant synthesis and accumulation of atractylenolides and the higher enzymes activities were described on the eight day after fungal elicitor inoculation than the control group. Furthermore, the treatments of A. maceocephalae seedlings with P. S.rolfsii increased disease index development caused by S. rolfsii . The disease index is lowest when inoculated at a concentration as low as 20 mg/ml. In general, these results indicated that P. S. rolfsii may be useful as a fungal elicitor, which can enhance resistance and triggered innate immunity in A . maceocephalae , and had the potential to suppress the disease on A. maceocephalae when P. S. rolfsii at 20 mg/l, were used to inoculate the root of A . maceocephalae. [ABSTRACT FROM AUTHOR]

Drugs that exhibit a high degree of tumor cell selectivity while minimizing normal cell toxicity are an area of active research interest as a means of designing novel antitumor agents. The pharmacological benefits of Chinese herbal medicine-based treatments have been the focus of growing research interest in recent years. Sesquiterpenoids derived from the Atractylodes macrocephala volatile oil preparations exhibit in vitro and in vivo antitumor activity. Atracylenolides exhibit anti-proliferative, anti-metastatic, and immunomodulatory activity in a range of tumor cell lines in addition to being capable of regulating metabolic activity such that it is a promising candidate drug for the treatment of diverse cancers. The present review provides a summary of recent advances in Atractylenolide-focused antitumor research efforts. [Display omitted] • Atractyloides belong to sesquiterpenoids. • Antitumor effects of Atractylodes involve nine cancers. • Atractylodes inhibits tumor growth, metastasis, chemoresistance and immune escape. • Atractylodes with high efficacy and low toxicity has an adjuvant antitumor effect. • Atractylodes has the potential to improve the physical status of cancer patients. [ABSTRACT FROM AUTHOR]

Atractylenolides compounds (atractylenolide-I, atractylenolide- II and atractylenolide- III) extracted from Atractylenolides macrocephala were analysed for their differential presence in the rhizome of both the infected and healthy plants and its fungitoxicity on prophylactic treatment with polysaccharides of Chrysanthemum indicum against Sclerotium rolfsii. It was evident that the plant under stress by pathogen has instigated the significant synthesis and accumulation of atractylenolide- II and atractylenolide- III in the rhizome of plants as a result of elicitation with polysaccharides of C. indicum. Our results also showed that the absence of atractylenolide- II in the rhizome made the plant susceptible to S. rolfsii. Furthermore, on in vitro antifungal studies, exogenous application of atractylenolide- II with the concentration of 200 μg/ml showed a significant inhibitory effect on mycelial growth by achieving a 77.23% antifungal activity rate, and a minimal inhibitory effect at a concentration of 12.5 μg/ml with atractylenolide- II. To our knowledge, this novel study on phytoalexins in A. macrocephala suggested that A. macrocephala plants produce elevated levels of atractylenolide- II and atractylenolide- III in a pattern typical of phytoalexins, in response to an eliciting treatment after infection. [ABSTRACT FROM AUTHOR]

Total synthesis of seven bioactive atractylenolide-type eudesmanolides from Hagemann’s ester, following, a short, scalable, adaptable, and diversity oriented protocol, has been accomplished. This effort opens a gateway to access through synthesis an exceptionally potent and promising group of natural products and their congeners of contemporary interest. [ABSTRACT FROM AUTHOR]

The rhizome of the plant Atractylodes macrocephala Koidz is the major constituent of the Traditional Chinese Medicine Baizhu, frequently used to treat gastro-intestinal diseases. Many traditional medicine prescriptions based on Baizhu and the similar preparation Cangzhu are used in China, Korea and Japan as Qi-booster. These preparations contain atractylenolides, a small group of sesquiterpenoids endowed with antioxidant and anti-inflammatory properties. Atractylenolides I, II and III also display significant anticancer properties, reviewed here. The capacity of AT-I/II/IIII to inhibit cell proliferation and to induce cancer cell death have been analyzed, together with their effects of angiogenesis, metastasis, cell differentiation and stemness. The immune-modulatory properties of ATs are discussed. AT-I has been tested clinically for the treatment of cancer-induced cachexia with encouraging results. ATs, alone or combined with cytotoxic drugs, could be useful to treat cancers or to reduce side effects of radio and chemotherapy. Several signaling pathways have been implicated in their multi-targeted mechanisms of action, in particular those involving the central regulators TLR4, NFκB and Nrf2. A drug-induced reduction of inflammatory cytokines production (TNFα, IL-6) also characterizes these molecules which are generally weakly cytotoxic and well tolerated in vivo. Inhibition of Janus kinases (notably JAK2 and JAK3 targeted by AT-I and AT-III, respectively) has been postulated. Information about their metabolism and toxicity are limited but the long-established traditional use of the Atractylodes and the diversity of anticancer effects reported with AT-I and AT-III should encourage further studies with these molecules and structurally related natural products. • Atractylenolides have been isolated from the rhizomes of Atractylodes species. • The Chinese medicines Baizhu and Cangzhu, containing atractylenolides, are used to treat gastro-intestinal diseases. • The pharmacological properties and anticancer activities of atractylenolides are reviewed here. • These products display marked anticancer effects against multiple tumor indications. • Inhibition of Janus kinases and down-regulation of IL-6 are major mechanistic components. [ABSTRACT FROM AUTHOR]