Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease (CBSinIIDD)

Summary

According to the records of traditional Chinese medicine, CBS has the following functions: clearing the heart, resolving phlegm, promoting bile secretion, and calming the nerves. It can treat fever, coma, delirium, epilepsy, convulsions in children, dental caries, throat swelling, oral sores, carbuncle, and furuncle. The significant pathophysiological process of primary inflammatory demyelinating disease of the central nervous system (hereinafter referred to as IIDD) is the activation of the immune system of the central nervous system and the enhancement of inflammation. It includes several common diseases: multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-related disease (MOGAD), acute disseminated encephalomyelitis (ADEM), concentric sclerosis, tumor-like inflammatory demyelinating disease, etc. Combined with the inspiration brought to us by the above background research, especially bilirubin and bile acid are closely related to intestinal digestive function, and CBS is clinically effective through oral administration by subjects, the investigators speculate that CBS is likely to exert its immune, anti-inflammatory and neuroprotective effects on the brain by changing the intestinal flora and regulating the brain-gut axis. In terms of symptoms, CBS is likely to have the effect of improving the clinical symptoms of IIDD subjects and reducing disability.

Timeline

Start

2024-08-08

Primary completion

2029-07

Completion

2029-12

Publications

• Background Fu WJ, Lei T, Yin Z, Pan JH, Chai YS, Xu XY, Yan YX, Wang ZH, Ke J, Wu G, Xu RH, Paranjpe M, Qu L, Nie H. Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis. J Ethnopharmacol. 2017 Jan 4;195:118-126. doi: 10.1016/j.jep.2016.11.015. Epub 2016 Nov 20.
• Background Zhou J, Jiang T, Wang J, Wu W, Duan X, Jiang H, Jiao Z, Wang X. Multimodal investigation reveals the neuroprotective mechanism of Angong Niuhuang pill for intracerebral hemorrhage: Converging bioinformatics, network pharmacology, and experimental validation. J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117045. doi: 10.1016/j.jep.2023.117045. Epub 2023 Aug 24.
• Background Yu ZJ, Xu Y, Peng W, Liu YJ, Zhang JM, Li JS, Sun T, Wang P. Calculus bovis: A review of the traditional usages, origin, chemistry, pharmacological activities and toxicology. J Ethnopharmacol. 2020 May 23;254:112649. doi: 10.1016/j.jep.2020.112649. Epub 2020 Feb 14.
• Background Shi Y, Xiong J, Sun D, Liu W, Wei F, Ma S, Lin R. Simultaneous quantification of the major bile acids in artificial Calculus bovis by high-performance liquid chromatography with precolumn derivatization and its application in quality control. J Sep Sci. 2015 Aug;38(16):2753-62. doi: 10.1002/jssc.201500139. Epub 2015 Jun 30.
• Background Shimada K, Azuma Y, Kawase M, Takahashi T, Schaffer SW, Takahashi K. Taurine as a marker for the identification of natural Calculus Bovis and its substitutes. Adv Exp Med Biol. 2013;776:141-9. doi: 10.1007/978-1-4614-6093-0_15.
• Background Li X, Yao Y, Chen M, Ding H, Liang C, Lv L, Zhao H, Zhou G, Luo Z, Li Y, Zhang H. Comprehensive evaluation integrating omics strategy and machine learning algorithms for consistency of calculus bovis from different sources. Talanta. 2022 Jan 15;237:122873. doi: 10.1016/j.talanta.2021.122873. Epub 2021 Sep 30.
• Background Liu Y, Tan P, Liu S, Shi H, Feng X, Ma Q. A new method for identification of natural, artificial and in vitro cultured Calculus bovis using high-performance liquid chromatography-mass spectrometry. Pharmacogn Mag. 2015 Apr-Jun;11(42):304-10. doi: 10.4103/0973-1296.153083.
• Background Tang Y, Han Z, Zhang H, Che L, Liao G, Peng J, Lin Y, Wang Y. Characterization of Calculus bovis by principal component analysis assisted qHNMR profiling to distinguish nefarious frauds. J Pharm Biomed Anal. 2023 May 10;228:115320. doi: 10.1016/j.jpba.2023.115320. Epub 2023 Mar 1.
• Background Takahashi K, Azuma Y, Shimada K, Saito T, Kawase M, Schaffer SW. Quality and safety issues related to traditional animal medicine: role of taurine. J Biomed Sci. 2010 Aug 24;17 Suppl 1(Suppl 1):S44. doi: 10.1186/1423-0127-17-S1-S44.
• Background Lu F, Wang L, Chen Y, Zhong X, Huang Z. In vitro cultured calculus bovis attenuates cerebral ischaemia-reperfusion injury by inhibiting neuronal apoptosis and protecting mitochondrial function in rats. J Ethnopharmacol. 2020 Dec 5;263:113168. doi: 10.1016/j.jep.2020.113168. Epub 2020 Jul 27.
• Background Zhong XM, Ren XC, Lou YL, Chen MJ, Li GZ, Gong XY, Huang Z. Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats. J Ethnopharmacol. 2016 Nov 4;192:390-397. doi: 10.1016/j.jep.2016.09.014. Epub 2016 Sep 9.
• Background Vitek L, Tiribelli C. Bilirubin: The yellow hormone? J Hepatol. 2021 Dec;75(6):1485-1490. doi: 10.1016/j.jhep.2021.06.010. Epub 2021 Jun 18.
• Background Thakkar M, Edelenbos J, Dore S. Bilirubin and Ischemic Stroke: Rendering the Current Paradigm to Better Understand the Protective Effects of Bilirubin. Mol Neurobiol. 2019 Aug;56(8):5483-5496. doi: 10.1007/s12035-018-1440-y. Epub 2019 Jan 5.
• Background Vasavda C, Kothari R, Malla AP, Tokhunts R, Lin A, Ji M, Ricco C, Xu R, Saavedra HG, Sbodio JI, Snowman AM, Albacarys L, Hester L, Sedlak TW, Paul BD, Snyder SH. Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide. Cell Chem Biol. 2019 Oct 17;26(10):1450-1460.e7. doi: 10.1016/j.chembiol.2019.07.006. Epub 2019 Jul 25.
• Background Liu HW, Gong LN, Lai K, Yu XF, Liu ZQ, Li MX, Yin XL, Liang M, Shi HS, Jiang LH, Yang W, Shi HB, Wang LY, Yin SK. Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage. Neuron. 2023 May 17;111(10):1609-1625.e6. doi: 10.1016/j.neuron.2023.02.022. Epub 2023 Mar 14.
• Background Bhargava P, Smith MD, Mische L, Harrington E, Fitzgerald KC, Martin K, Kim S, Reyes AA, Gonzalez-Cardona J, Volsko C, Tripathi A, Singh S, Varanasi K, Lord HN, Meyers K, Taylor M, Gharagozloo M, Sotirchos ES, Nourbakhsh B, Dutta R, Mowry EM, Waubant E, Calabresi PA. Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation. J Clin Invest. 2020 Jul 1;130(7):3467-3482. doi: 10.1172/JCI129401.
• Background Li CX, Wang XQ, Cheng FF, Yan X, Luo J, Wang QG. Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro. Neural Regen Res. 2019 Nov;14(11):1941-1949. doi: 10.4103/1673-5374.259617.
• Background Khalaf K, Tornese P, Cocco A, Albanese A. Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases. Transl Neurodegener. 2022 Jun 4;11(1):33. doi: 10.1186/s40035-022-00307-z.
• Background Hurley MJ, Bates R, Macnaughtan J, Schapira AHV. Bile acids and neurological disease. Pharmacol Ther. 2022 Dec;240:108311. doi: 10.1016/j.pharmthera.2022.108311. Epub 2022 Nov 16.
• Background Jangra A, Gola P, Singh J, Gond P, Ghosh S, Rachamalla M, Dey A, Iqbal D, Kamal M, Sachdeva P, Jha SK, Ojha S, Kumar D, Jha NK, Chopra H, Tan SC. Emergence of taurine as a therapeutic agent for neurological disorders. Neural Regen Res. 2024 Jan;19(1):62-68. doi: 10.4103/1673-5374.374139.
• Background Liu K, Zhu R, Jiang H, Li B, Geng Q, Li Y, Qi J. Taurine inhibits KDM3a production and microglia activation in lipopolysaccharide-treated mice and BV-2 cells. Mol Cell Neurosci. 2022 Sep;122:103759. doi: 10.1016/j.mcn.2022.103759. Epub 2022 Jul 25.
• Background Ohsawa Y, Hagiwara H, Nishimatsu SI, Hirakawa A, Kamimura N, Ohtsubo H, Fukai Y, Murakami T, Koga Y, Goto YI, Ohta S, Sunada Y; KN01 Study Group. Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial. J Neurol Neurosurg Psychiatry. 2019 May;90(5):529-536. doi: 10.1136/jnnp-2018-317964. Epub 2018 Apr 17.
• Background Martinez-Vacas A, Di Pierdomenico J, Gallego-Ortega A, Valiente-Soriano FJ, Vidal-Sanz M, Picaud S, Villegas-Perez MP, Garcia-Ayuso D. Systemic taurine treatment affords functional and morphological neuroprotection of photoreceptors and restores retinal pigment epithelium function in RCS rats. Redox Biol. 2022 Nov;57:102506. doi: 10.1016/j.redox.2022.102506. Epub 2022 Oct 14.
• Background Zhang F, Deng Y, Wang H, Fu J, Wu G, Duan Z, Zhang X, Cai Y, Zhou H, Yin J, He Y. Gut microbiota-mediated ursodeoxycholic acids regulate the inflammation of microglia through TGR5 signaling after MCAO. Brain Behav Immun. 2024 Jan;115:667-679. doi: 10.1016/j.bbi.2023.11.021. Epub 2023 Nov 19.

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