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Evaluation of Rhododendri Mollis Flos and its representative component as a potential analgesic

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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.

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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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Author notes

  1. Xin Wang and Wenjing Guo have contributed equally to this work.

Authors and Affiliations

  1. Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Xin Wang, Wenjing Guo, Bo Zhang, Qingyun Yang, Jingyi Zhao, Yi Feng, Jian Yang & Jiquan Zhang

  2. Suzhou Kaixiang Biotechnology Co. LTD, Suzhou, 215600, China

    Haixia Xu

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  1. Xin Wang
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Contributions

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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Correspondence to Jian Yang or Jiquan Zhang.

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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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