Abstract
Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 μM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.
Graphical abstract
Abbreviations
- AA:
-
Glacial acetic acid
- ALB:
-
Albumin
- ALP:
-
Alkaline phosphatase
- ALT:
-
Alanineaminotra ferase
- ASA:
-
Aspirin
- AST:
-
Aspartate aminotransferase
- B:
-
Basophilic granulocyte
- CCI:
-
Chronic constriction injury model
- CI:
-
Confidence interval
- CHOL:
-
Total cholesterol
- CK:
-
Creatine kinase
- CRE:
-
Creatinine
- DMSO:
-
Dimethyl sulfoxide
- E:
-
Eosinophils
- EGTA:
-
Ethylene glycol-bis-(2-amino-ethylether)-N,N,N′,N′-tetraacetic acid
- GBP:
-
Gabapentin
- GGT:
-
Gamma-glutamyltransferase
- GLU:
-
Blood glucose
- HCT:
-
Red blood cell specific volume
- HEPES:
-
N-2-hydroxyethylpiperazine-N-2-ethane sulfonic acid
- HGB:
-
Hemoglobin
- L:
-
Lymphocyte
- M:
-
Monocytes
- MCH:
-
Mean corpuscular hemoglobin
- MCHC:
-
Mean corpuscular hemoglobin concentration
- MCV:
-
Mean corpuscular volume
- MED:
-
Minimum effective dose
- N:
-
Neutrophil
- PLT:
-
Platelet count
- PTWL:
-
Paw thermal withdrawal latency
- PMWT:
-
Paw mechanical withdrawal threshold
- RBC:
-
Red blood cell
- Ret:
-
Reticulocyte count
- R. mole Flos:
-
Rhododendri Mollis Flos
- RJ-III:
-
Rhodojaponin III
- RJ-VI:
-
Rhodojaponin VI
- TBIL:
-
Total bilirubin
- TG:
-
Triglyceride
- TP:
-
Total protein
- Urea:
-
Blood urea nitrogen
- WBC:
-
White blood cell
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Acknowledgements
We would like to thank Shanghai University of Traditional Chinese Medicine and Shanghai Institute of Materia Medica, Chinese Academy of Sciences for their help in terms of equipment and facilities.
Funding
The work was supported by the Science and Technology Commission of Shanghai Municipality (Grant No. 23S21900300 and No. 14401901400) and the Shanghai Municipal Commission of Health and Family Planning (Grant No. ZY (2021–2023)-0208).
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Xin Wang: investigation, data analysis. Wenjing Guo: investigation and data analysis. Bo Zhang, Haixia Xu, Qingyun Yang and Jingyi Zhao: investigation. Yi Feng: supervision and funding acquisition. Jian Yang: investigation, data analysis, visualization, and writing—original draft. Jiquan Zhang: conceptualization, project administration, and supervision. All authors read and approved the final manuscript. m15110357908@163.com; 503,666,853@qq.com; zb15670581612@163.com; haixiaxu@hotmail.com; yqy_1117@163.com; 448,403,430@qq.com; fyi@vip.sina.com; Yjsmile2018@163.com; jqzhang@shutcm.edu.cn.
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Wang, X., Guo, W., Zhang, B. et al. Evaluation of Rhododendri Mollis Flos and its representative component as a potential analgesic. J Nat Med 78, 753–767 (2024). https://doi.org/10.1007/s11418-024-01815-0
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DOI: https://doi.org/10.1007/s11418-024-01815-0