Toxicity of “Aconitum Carmichaelii-Pinellia Ternata” Incompatible Combination: a Systematic Review and Meta-Analysis of Experimental Studies on Rats

doi:10.19803/j.1672-8629.20240438

Abstract

Abstract: Objective To systematically assess the toxicity of “aconitum carmichaelii-pinellia ternate” incompatible combination in rats. Methods CNKI, Wanang database, VIP, SinoMed, PubMed, Embase and Web of Science database were searched for related literature on toxicity of “aconitum carmichaelii-pinellia ternate” incompatible combination in rats that was published from inception to April 3, 2024. Two reviewers independently screened the literature, retrieved the data, and used the SYRCLE animal experiment bias risk assessment tool to evaluate risk bias before turning to RevMan 5.4 software for meta-analysis. Results A total of 13 experiments were included in this study. The results of meta-analysis showed that compared with the blank control group, the compatibility between aconitum carmichaelii and pinellia ternata at the 1∶1 ratio made no much difference to the liver index or contents of ALT, Cr and BUN of normal rats. However, the cardiac index, kidney index, and contents of AST, ALP, CK and CK-MB were increased significantly. Compared with the aconitum carmichaelii used alone group, aconitum carmichaelii and pinellia ternata at the 1∶1 ratio could reduce the contents of AST, ALP, CK and kidney indexes rather than the cardiac indexes and CK-MB content. Compared with the blank control group, the compatibility of aconiti lateralis radix praeparata and pinellia ternata at the 1∶1 ratio led to a significant increase of the CK content alone, but could reverse the change of CK levels in model rats compared with ischemia-reperfusion injury model rats. The results of qualitative analysis showed that the aconitum carmichaelii and pinellia ternata compatibility had no effect on or caused only mild injury to the histopathology of the heart, liver and kidney of normal rats. However, the aconiti lateralis radix praeparata and pinellia ternata compatibility could mitigate the cardiac pathological injury in rats in the cardiac pathological model. Conclusion The compatibility between aconitum carmichaelii and pinellia ternata at the 1∶1 ratio has some effect on liver, heart and kidney parameters in normal rats by alleviating the hepatic and renal injuries induced by aconitum carmichaelii alone, but exerts minimal effect on the cardiac damage caused by aconitum carmichaelii. Such compatibility has a protective effect on cardiac pathological model rats. Therefore, the incompatible combination of aconitum carmichaelii and pinellia ternata has to be used with caution. Aconiti lateralis radix praeparata and pinellia ternate may achieve good effects once accurate diagnosis and proper prescriptions are ensured.

Key words: Aconitum Carmichaelii, Pinellia Ternata, Eighteen Antagonisms, Rats, Toxicity, Meta-Analysis

CLC Number:

R994.11

WANG Ping, CAO Huijuan, LI Mengqi, ZHANG Guozhi, LIU Jianping, JIN Xuejing. Toxicity of “Aconitum Carmichaelii-Pinellia Ternata” Incompatible Combination: a Systematic Review and Meta-Analysis of Experimental Studies on Rats[J]. Chinese Journal of Pharmacovigilance, 2025, 22(2): 177-182.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240438

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I2/177

References

[1] WANG F.Test and Refute the“Eighteen Contraries”Compatibility Taboos from the Perspective of Prescription and Prescription[J]. Traditional Chinese Medicine Journal(中医药通报), 2020, 19(5): 14-17.
[2] CHEN JJ, ZHANG NZ, XUE XM, et al.Literature Review and Reflection on the Contraindications of Compatibility Based on the Eighteen Antagonisms and Nineteen Inhibitions[J]. China’s Naturopathy(中国民间疗法), 2024, 32(7): 3-5.
[3] GE YT, XIAO QQ, GAO Y, et al.Feasibility of Combination of Antagonism Chinese Medicinals Based on the Theory of “Eighteen Antagonisms”[J]. Journal of Traditional Chinese Medicine(中医杂志), 2023, 64(17): 1734-1739.
[4] ZHU YX, LIN JZ, CHEN SH.Clinical Analysis Study on Traditional Chinese Medicine Prescriptions with Aconitum and Pinellia as Incompatible Drug Combination[J]. Journal of China Prescription Drug(中国处方药), 2022, 20(4): 138-140.
[5] SU FL, YAO Y, FENG SY, et al.Investigation and Analysis of 500 Outpatient Prescriptions of Aconiti Lateralis Radix Aconiti with Pinelliae Rhizoma, Fritillaria Bulbus and Trichosanthis Radix[J]. Chinese Journal of Hospital Pharmacy(中国医院药学杂志), 2024, 44(4): 451-455, 461.
[6] WANG LQ, WU CH, WANG TY, et al.The Key Points of Clinical Application of Fuzi and Banxia Based on TCM Shiceng Pulse Theory[J]. Clinical Journal of Chinese Medicine(中医临床研究), 2024,16(3): 128-131.
[7] GU H, MA YT, GUAN JJ, et al.A Clinical Study on the Combined Application of Processed Fuzi and Processed Banxia[J]. Clinical Journal of Chinese Medicine(中医临床研究), 2023, 15(22): 56-60.
[8] ZHANG LJ, WU X.Analysis on the Combined Use of Chinese Patent Medicines Contains Aconitum and Pinellia[J]. Chinese Traditional Patent Medicine(中成药), 2023, 45(5): 1745-1748.
[9] HU X, CHEN QL, JIN RY.Simultaneous Use and Application of Pinellia Rhizome and Radix Aconiti Lateralis from Perspective of Ancient and Modern[J]. Journal of Chengdu University of Traditional Chinese Medicine(成都中医药大学学报), 2024, 47(2): 46-50.
[10] Expert Group on Rational Evaluation and Improvement of Clinical Use of Traditional Chinese Medicine. The Expert Consensus on Classification of the Eighteen Incompatible Medic Aments and Nineteen Counteraction Theory and the Application in Clinical Safety Risk Assessment[J]. Herald of Medicine(医药导报), 2024, 43(6): 841-849.
[11] LIU J.Analyzing the Clinical Research Literature of Eighteen Incompatible Herbs with“Banxia Wutou”Class Anti-Drug Compatibility Combination from the Perspective of Evidence-Based Medicine[D]. Beijing: Beijing University of Chinese Medicine, 2015.
[12] LIU G.Observation of Long-Term Toxicity of Compatibility Combination Chuanwu and Fabanxia in Rats[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy(中国民族民间医药), 2010, 19(20): 42-43.
[13] XU L, TONG JM, YANG HB, et al.Toxicity of Raw Chuanwu Combined with Raw Banxia in Different Proportions on Rat Myocardium[J]. Journal of Traditional Chinese Medicine(中医杂志), 2013, 54(12): 1043-1046.
[14] YANG KB, YIN CJ, TONG JM, et al.Liver Toxicity of Water Infusion of Anti-Drug Compatibility Combination Raw Chuanwu and Raw Banxia on Rats[J]. Chinese Traditional Patent Medicine(中成药), 2015, 37(2): 397-400.
[15] YANG KB, YIN CJ, TONG JM, et al.Impact on Renal Toxicity with the Compatibility of Different Proportions of raw Chuanwu (Aconitum Carmichaelii) and Raw Banxia (Pinellia ternata)[J]. Journal of Traditional Chinese Medicine(中医杂志), 2015, 56(2): 156-159.
[16] YANG KB, YIN CJ, ZHAO SM, et al.Effect of Raw Radix Aconite with Different Proportions of Raw Penillia Ternate on the Ultrastrueture of Livers in Rats[J]. Chinese Journal of Anatomy(解剖学杂志), 2016, 39(4): 406-408.
[17] YANG KB, YIN CJ, ZHAO SM, et al.Effect of Aqueous Extract from Raw Radix Aconite on Ultrastructure of Rat Kidney and its Relationship with Compatibility Ratio of Raw Penillia Ternate[J]. Chinese Journal of Anatomy(解剖学杂志), 2016, 39(5): 557-560.
[18] ZHANG Q.The Chemical Fundamental Substances and Toxicity Mechanism of the Eighteen Incompatible Pairs about“Pinellia Tuber, Trichosanthes Fructus, Fritillaria, Ampelosis Radix, Common Bletilla Tuber Attack Radix Aconiti”[D]. Changchun: Changchun University of Chinese Medicine, 2010.
[19] LI L, MA YH, OUYANG JP.Studies on Compatibility of Radix Aconiti Lateralis Preparatae with Rhizoma Pinelliae in Rat Model[J]. Chinese Journal of Modern Drug Application(中国现代药物应用), 2009, 3(5): 5-7.
[20] ZHAO ZH, ZHOU Y, ZHANG XM, et al.Study on Toxicity Effects of Different Compatibility Proportions of Aconite and Pinellia on Rats[J]. Journal of Liaoning University of Traditional Chinese Medicine(辽宁中医药大学学报), 2014, 16(2): 36-38.
[21] LI L, HUANG CF, MA YH, et al.Effects of Monkshood and Pinellia Preconditioning on SOD, MDA and Apoptosis in Rats with Myocardial Ischemia-Reperfusion Injury[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2013, 29(2): 97-100.
[22] LI L, MA YH, HUANG CF, et al.Effects of Monkshood and Pinellia Preconditioning on Cardiac Function and Myocardial Ultrastructure in Rats with Myocardial Ischemia-Reperfusion Injury[J]. Lishizhen Medicine and Materia Medica Research(时珍国医国药), 2014, 25(2): 325-327.
[23] SUN FJ, HUANG YY, LI LL, et al.Fuzi and Banxia Combination, Eighteen Antagonisms in Chinese Medicine, Aggravates Adriamycin-Induced Cardiomyopathy Associated with PKA/β2AR-Gs Signaling[J]. Evidence-Based Complementary and Alternative Medicine, 2018, 2018: 2875873.
[24] SUN FJ, HUANG YY, LI LL, et al.PKA/β2-AR-Gs/Gi Signaling Pathway is Associated with Anti-Inflammatory and Pro-Apoptotic Effects of Fuzi and Banxia Combination on Rats Subjected to Pressure Overload[J]. Journal of Ethnopharmacology, 2019, 235: 375-384.
[25] FAN XS, DUAN JA, HUA HM, et al.Study on Incompatibility of Traditional Chinese Medicines[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2015, 40(8): 1630-1634.
[26] Chinese Pharmacopocia Commission.Pharmacopoeia of the People’s Republic of China: Volume I(中华人民共和国药典一部)[M]. Beijing: China Medical Science Press, 2020.
[27] TENG PY.Study on the Compatibility’ Acute Toxicity Test and Pharmacodynamics of Aconite and Pinellia[D]. Guangzhou: Guangzhou University of Chinese Medicine, 2017.
[28] ZHANG T, ZHUANG PW, LAI XY, et al.Acute Toxicity Studies on Compatibility of“Pinellia, Trichosanthes, Fritillaria, Ampelopsis, Bletilla Attack Aconitum”[J]. Chinese Traditional and Herbal Drugs(中草药), 2013, 44(17): 2442-2445.
[29] WANG D, HE QY, DAN WC, et al.Mapping Knowledge Domain Analysis on TCM Treatment for Edema[J]. Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology(世界科学技术-中医药现代化), 2022, 24(11): 4149-4159.
[30] ZHANG C, LENG MY, RAO AY, et al. Medicinal Properties and Effects of Aconitum Carmichaelii: Based on the Theory of Multiple Medicines Derived from One Plant[J/OL]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床),(2024-07-18)[2024-08-06]. https://
doi.org/10.13412/j.cnki.zyyl.20240716.002.
[31] JEON SY, JEONG W, PARK JS, et al.Clinical Relationship between Blood Concentration and Clinical Symptoms in Aconitine Intoxication[J]. Am J Emerg Med, 2021, 40: 184-187.
[32] ZHANG S, YANG H, CHEN SQ, et al.Research Progress on Toxicity and Toxicokinetics of Aconitum[J]. Chinese Archives of Traditional Chinese Medicine(中华中医药学刊), 2024, 42(8): 232-236.
[33] QIAO PF.Analysis of Risk Factors for Acute Aconitine Poisoning to Malignant Arrhythmia[D]. Kunming: Kunming Medical University, 2023.
[34] FENG Q, YAO JC, LI X, et al.Network Toxicological Analysis and Mechanism Prediction of Cardiotoxicity of Alkaloids in Aconiti Radix[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2022, 19(1): 62-68.
[35] ZHOU YL, YANG P, LI XX, et al.Research Progress on Chemical Constituents and Pharmacological Effects of Pinelliae Rhizoma and its Quality Marker Prediction Analysis[J]. Chinese Traditional and Herbal Drugs(中草药), 2024, 55(14): 4939-4952.
[36] GUO HN, LI HH, JIANG MM, et al.Chemical Constituents of Pinellia Ternate(Thunb.) Breit[J]. Chinese Pharmaceutical Journal(中国药学杂志), 2024, 59(3): 235-240.
[37] YANG FJ, CHEN J, LI HD, et al.Research Progress on Toxic Components and Attenuated Processing Methods of Pinellia Ternate[J]. Feed Industry(饲料工业), 2023, 44(7): 94-98.
[38] LI ME, CHEN TC, MA YJ, et al.Research on Relative Toxicity Marking Model of Pinellia Ternata Processed Products[J]. Chinese Traditional and Herbal Drugs(中草药), 2022, 53(6): 1751-1760.
[39] TAO XB.Study on the Detoxification Mechanism by Processing, Phlegm-Relieving Effect and Related Material Basis of Pinelliae Rhizoma Praeparatum[D]. Nanjing: Nanjing University of Chinese Medicine, 2022.
[40] HUANG YM, LI CH, BAI JH, et al.Analysis of Pinellia Ternate Toxic Lectin Protein during Processing by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry[J]. Journal of Chinese Mass Spectrometry Society(质谱学报), 2024, 45(2): 226-236.
[41] SUN JH.Research Progress on the Processing and Compatibility of Toxic Aconitum Traditional Chinese Medicines to Reduce Toxicity[J]. World Journal of Complex Medicine(世界复合医学), 2024, 10(3): 195-198.
[42] WANG L, LIU R, XING S, et al.Comparative study on UPLC/Q–TOF–MS Ion Flow Diagram, OPLS–DA/PCS and Differential Compounds between Radix Polygoni and Rhizoma Pinelliae and Pinellia Ternata and Pinellia Ternate[J]. Journal of Sichuan of Traditional Chinese Medicine(四川中医), 2020, 38(1): 58-62.
[43] ZHAI J, MAN VH, JI B, et al.Comparison and Summary of in Silico Prediction Tools for CYP450-Mediated Drug Metabolism[J]. Drug Discov Today, 2023, 28(10): 103728.
[44] WU JJ, CHENG ZX, ZHU LJ, et al.Coadministration of Pinellia Ternata can Significantly Reduce Aconitum Carmichaelii to Inhibit CYP3A Activity in Rats[J]. Evid Based Complement Alternat Med, 2014, 2014: 734867.
[45] JIN KT, SHI SY, SHEN JX, et al.The Regulating Effect of Aconitum Coadministration with Pinellia on Cytochrome P450 in Rat Livers[J]. Chinese Archives of Traditional Chinese Medicine(中华中医药学刊), 2007, 25(7): 1358-1361.
[46] AN ZJ, ZHANG KY, ZHOU MJ, et al.Study on the Material Basis and Mechanism on Glycyrrhiza Co-Administered with Sargassum Pallidum, Euphorbia Pekinensis, Euphorbia Kansui and Daphne Genkwa Incompatibility[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2023, 20(12): 1435-1440.
[47] TIAN Y, LI MY, CAO C, et al.Research Status and Thinking on “Eighteen Antagonisms”Based on Toxic-Effect Relationship[J]. China Journal of Traditional Chinese Medicine and Pharmacy(中华中医药杂志), 2023, 38(4): 1426-1430.
[48] SHI Z.Study on Active/Toxic Components and Mechanism of Aconitum Carmichaeli Based on Network Pharmacology and Molecular Docking[D]. Chengdu: University of Electronic Science and Technology of China, 2021.
[49] LI S, SHU JQ, XIAO WK, et al.Exploration on Characteristics of Decocting Ratio of Monoester Aconitum Alkaloid of Aconiti Radix in Different Compatibility by Knowledge Map[J]. China Journal of Traditional Chinese Medicine and Pharmacy(中华中医药杂志), 2022, 37(6): 3171-3176.