Exploring the Scientific Connotation of Gypsum in Baihu Decoction Compatibility with Heat-clearing Effect Based on Phase Composition

Yunyun Wang; Zhengxian Zhang; Haotian Peng; Huahui Zeng; Xiangxiang Wu

doi:10.1055/s-0045-1807263

Chinese medicine and natural products, Table of Contents

CC BY 4.0 · Chinese medicine and natural products 2025; 05(01): e35-e46
DOI: 10.1055/s-0045-1807263

Original Article

Exploring the Scientific Connotation of Gypsum in Baihu Decoction Compatibility with Heat-clearing Effect Based on Phase Composition

Authors

Yunyun Wang

¹Collaborative Innovation Center for the Development of the Entire Henan Medicinal Industry Chain, Henan University of Chinese Medicine, Zhengzhou, Henan, China
Zhengxian Zhang

¹Collaborative Innovation Center for the Development of the Entire Henan Medicinal Industry Chain, Henan University of Chinese Medicine, Zhengzhou, Henan, China
Haotian Peng

¹Collaborative Innovation Center for the Development of the Entire Henan Medicinal Industry Chain, Henan University of Chinese Medicine, Zhengzhou, Henan, China
Huahui Zeng

¹Collaborative Innovation Center for the Development of the Entire Henan Medicinal Industry Chain, Henan University of Chinese Medicine, Zhengzhou, Henan, China
Xiangxiang Wu

¹Collaborative Innovation Center for the Development of the Entire Henan Medicinal Industry Chain, Henan University of Chinese Medicine, Zhengzhou, Henan, China

Abstract

Objective

This study aimed to study the effects of different crystalline states of Sheng Shigao (raw gypsum, RG) and its inorganic elements on the antipyretic efficacy of Baihu Decoction (BHT).

Methods

RG samples calcined at different temperatures were prepared. The phase composition of RG and Duan Shigao (calcination of gypsum, CG) as well as the changes in phase composition before and after adding water to RG calcined at specific temperatures, were determined using X-ray diffraction (XRD). A fever model was established by subcutaneously injecting 20% yeast suspension (10 mL·kg⁻¹) into the backs of rats. The effects of BHT containing RG in different crystalline states on rat body temperature were measured. Serum levels of IL-1β, IL-6, and hypothalamic prostaglandin E2 (PGE₂) were detected using ELISA. Serum Ca²⁺ levels were measured using a microplate method. The content of trace elements in RG and CG and the corresponding freeze-dried BHT powder was determined using inductively coupled plasma mass spectrometry (ICP-MS). The complexation of representative inorganic elements with mangiferin, a major active component in BHT, was investigated using UV-Vis spectroscopy and fluorescence spectroscopy. A validation model was established using RAW264.7 mouse macrophages. Drug-containing serum of BHT with different inorganic elements was prepared, and the nitric oxide (NO) levels in the cell supernatant of different treatment groups were measured using the Griess method. The mRNA levels of IL-6, TNF-α, and PGE₂ in each group were detected using qPCR (real-time fluorescent quantitative PCR).

Results

After calcination, the phase composition of RG changed, and the content of inorganic elements in RG, CG170 (RG calcined at 170 °C), and CG350 (RG calcined at 350 °C) showed similar trends. Compared with RG, the content of Ca, Sr, Al, and Na in CG changed significantly. Compared with BHT, the content of Ca, Sr, Si, and Na in CG changed significantly when incorporated into the formula. Intermolecular interactions confirmed strong binding between mangiferin and Cu²⁺ and Al³⁺. Cu²⁺ and Fe³⁺ exhibited fluorescence quenching effects on mangiferin solution, while Al³⁺ and Zn²⁺ showed strong fluorescence enhancement, with fluorescence intensity increasing by 120-fold and 30-fold, respectively. In vitro evaluation of synergistic anti-inflammatory effects confirmed that Ca, Fe, Cr, Al, and Si exhibited synergistic anti-inflammatory effects.

Conclusion

The crystalline state of RG has little effect on its antipyretic properties, while Ca, Sr, Na, Fe, and Al are likely the key material bases influencing its efficacy.

Keywords

gypsum - Baihu Decoction - heat-clearing - compatibility of medicines - phase composition

Full Text

References

References
1 National Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China. China Medical Science Press; 2020
2 Li Q, Li SS, Zhang H. Research on processing mechanism of water grinding on Realgar. Chin Tradit Herbal Drugs 2023; 54 (23) 7751-7758
3 Li Y. Effect of Calcining Temperature on Physicochemical Properties and Pharmacological Action of gypsum. Beijing: Beijing University of Chinese Medicine; 2017
4 Lü S, Su H, Sun S. et al. Isolation and characterization of nanometre aggregates from a Bai-Hu-Tang decoction and their antipyretic effect. Sci Rep 2018; 8 (01) 12209
5 Ping Y, Li Y, Lü S. et al. A study of nanometre aggregates formation mechanism and antipyretic effect in Bai-Hu-Tang, an ancient Chinese herbal decoction. Biomed Pharmacother 2020; 124: 109826
6 Guo Z. Separation and Characterization of Gegen-qin-lian Decoction. Fuzhou: Fuzhou University; 2014
7 Zhang F, Wang D, Li X, Li Z, Chao J, Qin X. Metabolomic study of the fever model induced by baker's yeast and the antipyretic effects of aspirin in rats using nuclear magnetic resonance and gas chromatography-mass spectrometry. J Pharm Biomed Anal 2013; 81-82: 168-177
8 Tian TY, Bao YR, Meng XS. Analysis of inorganic elements in gypsum fibrosum from different origins based on ICP-MS. Zhonghua Zhongyiyao Xuekan 2017; 35 (04) 1041-1043
9 Wang W, Zhou CX, Zhang YS. Comparative analysis of trace elements in gypsum from different regions. Chin Pharm 2014; 17 (06) 972-974
10 Tang J, Zhang Q, Wu D. et al. Potential pharmacodynamic substances of Laportea bulbifera in treatment of rheumatoid arthritis based on serum pharmacochemistry and pharmacology [in Chinese]. Zhongguo Zhongyao Zazhi 2022; 47 (17) 4755-4764
11 Wang F, Xiao M, Chen BC. The drug-containing serum of Suoquan Yishen Formula regulates the epithelial-mesenchymal transformation of glomerular podocytes by inhibiting KDM6A. Pharm Clin Chin Mater Med 2024; 40 (05) 8-14
12 Xie F, Jian GH, Dai BY. Investigation of the effect of drug-containing serum of Huoxi Decoction on chondrocyte pyroptosis based on CCL2/CCR2/NF-κB pathway. Pharm Clin Chin Mater Med 2024; 40 (05) 30-36
13 Qin MY, Huang SQ, Zou XQ. et al. Drug-containing serum of rhubarb-astragalus capsule inhibits the epithelial-mesenchymal transformation of HK-2 by downregulating TGF-β1/p38MAPK/Smad2/3 pathway. J Ethnopharmacol 2021; 280: 114414
14 Pan J, Jiang Y, Huang Y. et al. Liuwei Dihuang decoction drug-containing serum attenuates transforming growth factor-β1-induced epithelial-mesenchymal transition in HK-2 cells by inhibiting NF-κB/snail signaling pathway. Curr Pharm Biotechnol 2023; 24 (12) 1589-1602
15 Li CL. Standardized Study of Baihu Decoction. Nanjing: Nanjing University of Chinese Medicine; 2012
16 Tian HX. Effect of Polished Round-grained Rice on Composition and Function of Baihu decoction. Beijing: Beijing University of Chinese Medicine; 2022
17 Lin N. Effects of Different pH on Biological Activities and Colloidal Properties of Radix Isatidis Decoction (Banlangen). Fuzhou: Fuzhou University; 2011
18 Zhang Y, Li CJ. The effects of perfusion of lateral ventricle with CaCl2 on the febrile response and cAMP content in plasma and cerebrospinal fluid during LP-induced fever. Sci China B Chem Life Sci Earth Sci 1991; 34 (03) 317-326
19 Feldberg W, Myers RD, Veale WL. Perfusion from cerebral ventricle to cisterna magna in the unanaesthetized cat. Effect of calcium on body temperature. J Physiol 1970; 207 (02) 403-416
20 Song C, Zhang ZJ, Bian BL. Hypothesis on material basis of medicinal gypsum cooling. Guangpuxue Yu Guangpu Fenxi 2020; 40 (06) 1716-1721
21 Lin Y, Xin Z, Xia Y, Wen X, Xin F, Ruan G. Effect of strontium in drinking water on blood pressure and inflammatory function in hypertension mice [in Chinese]. Wei Sheng Yan Jiu 2023; 52 (04) 598-603
22 Buache E, Velard F, Bauden E. et al. Effect of strontium-substituted biphasic calcium phosphate on inflammatory mediators production by human monocytes. Acta Biomater 2012; 8 (08) 3113-3119
23 Duan S, Wang H, Gao Y, Wang X, Lyu L, Wang Y. Oral intake of titanium dioxide nanoparticles affect the course and prognosis of ulcerative colitis in mice: involvement of the ROS-TXNIP-NLRP3 inflammasome pathway. Part Fibre Toxicol 2023; 20 (01) 24
24 Zhang P, Lokuta KM, Turner DE, Liu B. Synergistic dopaminergic neurotoxicity of manganese and lipopolysaccharide: differential involvement of microglia and astroglia. J Neurochem 2010; 112 (02) 434-443
25 Liu CY, Han S, Tang YN. The hydration process of gypsum and its calcined products analyzed by low field nuclear magnetic resonance. J Beijing Tradit Chin Med 2021; 40 (10) 1157-1160
26 Farrin N, Rezazadeh L, Pourmoradian S. et al. Boron compound administration; A novel agent in weight management: A systematic review and meta- analysis of animal studies. J Trace Elem Med Biol 2022; 72: 126969
27 Kim EJ, Bu SY, Sung MK, Kang MH, Choi MK. Analysis of antioxidant and anti-inflammatory activity of silicon in murine macrophages. Biol Trace Elem Res 2013; 156 (1-3): 329-337
28 Moradi F, Maleki V, Saleh-Ghadimi S, Kooshki F, Pourghassem Gargari B. Potential roles of chromium on inflammatory biomarkers in diabetes: A systematic. Clin Exp Pharmacol Physiol 2019; 46 (11) 975-983
29 Tanhehco EJ. Potassium channel modulators as anti-inflammatory agents. Expert Opin Ther Pat 2001; 11 (07) 1137-1145
30 Mao X, Yan X, Li C, Liu Y, Zhang Y, Lin N. Extensive preclinical evaluation of combined mangiferin and glycyrrhizic acid for restricting synovial neovascularization in rheumatoid arthritis. Chin Med 2023; 18 (01) 156
31 Mao X, Liu Y, Li W. et al. A promising drug combination of mangiferin and glycyrrhizic acid ameliorates disease severity of rheumatoid arthritis by reversing the disturbance of thermogenesis and energy metabolism. Phytomedicine 2022; 104: 154216
32 Yang XD, Li GW, Wu WP. Effects of Anemarrhenae Rhizoma on the dissolution of 6 inorganic elements in gypsum fibrosum under different compatibility ratio based ongrey correlation analysis and TOPSIS model. Chin Pharm 2023; 26 (11) 346-354