Evaluation of Rhodojaponin III from Rhododendron molle G. Don on oral antinociceptive activity, mechanism of action, and subacute toxicity in rodents

Yang, Jian; Yang, Qingyun; Zhao, Jinfang; Sun, Shuigen; Liu, Minchen; Wang, Yuan; Feng, Yi; Zhang, Jiquan

doi:10.1016/j.jep.2022.115347

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…Zhou et al reported eight novel diterpenes compounds (26)(27)(28)(29)(30)(31)(32)(33) from the leaves of R. molle [9]. Additionally, Zhu et al identified seven new diterpenes (34)(35)(36)(37)(38)(39) from the leaves and twigs of R. decorum [25], with compounds 34, and 36-39 displaying significant antinociceptive activity at 10 mg/kg. Compound 38 was particularly potent, inhibiting 68.0% writhes at a dose of 0.8 mg/kg.…”

Section: Overview Of Structural Diversity and Biological Activities O...mentioning

confidence: 99%

“…One critical area for future research is the detailed mechanistic study of these compounds, especially regarding their therapeutic applications [7]. Grayanane diterpenes are known for their potent toxicity, which is primarily attributed to their mechanism of action on the sodium channels in the nervous system, leading to a cascade of neurotoxic effects [7,[37][38][39]. The limitations of using grayanane diterpenes stem from their narrow therapeutic index, the difficulty in controlling their dose-dependent toxic effects, and the potential for severe adverse reactions, including cardiac issues and central nervous system disturbances.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Recent Advances in Grayanane Diterpenes: Isolation, Structural Diversity, and Bioactivities from Ericaceae Family (2018–2024)

Liu,

Sun,

Zhang

et al. 2024

Molecules

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Diterpenes represent one of the most diverse and structurally complex families of natural products. Among the myriad of diterpenoids, grayanane diterpenes are particularly notable. These terpenes are characterized by their unique 5/7/6/5 tetracyclic system and are exclusive to the Ericaceae family of plants. Renowned for their complex structures and broad spectrum of bioactivities, grayanane diterpenes have become a primary focus in extensive phytochemical and pharmacological research. Recent studies, spanning from 2018 to January 2024, have reported a series of new grayanane diterpenes with unprecedented carbon skeletons. These compounds exhibit various biological properties, including analgesic, antifeedant, anti-inflammatory, and inhibition of protein tyrosine phosphatase 1B (PTP1B). This paper delves into the discovery of 193 newly identified grayanoids, representing 15 distinct carbon skeletons within the Ericaceae family. The study of grayanane diterpenes is not only a deep dive into the complexities of natural product chemistry but also an investigation into potential therapeutic applications. Their unique structures and diverse biological actions make them promising candidates for drug discovery and medicinal applications. The review encompasses their occurrence, distribution, structural features, and biological activities, providing invaluable insights for future pharmacological explorations and research.

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Section: Overview Of Structural Diversity and Biological Activities O...mentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Recent Advances in Grayanane Diterpenes: Isolation, Structural Diversity, and Bioactivities from Ericaceae Family (2018–2024)

Liu,

Sun,

Zhang

et al. 2024

Molecules

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“…However, its medicinal properties derived from the roots, flowers, and fruits remain relatively unknown. Extensive research has demonstrated that each medicinal component of this plant exhibits diverse effects such as anti-inflammatory and analgesic properties, antipyretic activity, and hypotensive effects [ 2 ]. Despite its therapeutic potential, it should be noted that Rhododendron molle possesses significant toxicity with no specific treatment available; hence, clinical management primarily focuses on symptomatic relief [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Notably, Rhodojaponin III surpasses morphine in terms of acute pain models as well as inflammatory pain models. Its potency for diabetic neuropathic pain models is 100 times greater than gabapentin's effectiveness [ 2 , 7 ]. However, it was discovered that both intraperitoneal administration and oral consumption of Rhodojaponin III resulted in severe acute toxicity in mice.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Rhodojaponin II and Rhodojaponin III in Rat Plasma by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry

Sun,

Wang,

Bao

et al. 2024

International Journal of Analytical Chemistry

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An ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method was developed to determine the concentrations of Rhodojaponin II and Rhodojaponin III in rat plasma, and their pharmacokinetic profiles were investigated. A UPLC HSS T3 (2.1 mm × 50 mm, 1.8 μm) chromatographic column was employed at a temperature of 40°C. The mobile phase consisted of acetonitrile‐0.1% formic acid in water, and a gradient elution method with an elution time of 6 min and flow rate of 0.4 mL/min was utilized for analysis purposes. Methodological investigations were conducted accordingly. The plasma concentrations of Rhodojaponin II and Rhodojaponin III exhibited excellent linearity within the range of 2 ng/mL–1250 ng/mL. Moreover, both intraday and interday precision were below 15%, while accuracy ranged from 88% to 115%. Additionally, matrix effect fell within the range of 90%–110%, and recoveries ranged from 78% to 87%. These results comply with relevant regulations for drug analysis in biological samples. Therefore, this method is deemed suitable for quantifying Rhodojaponin II and Rhodojaponin III levels in rats.

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“…Rhododendron molle G. Don, a Rhododendron genera plant of the Ericaceae family, is recorded as a toxic Chinese herbal medicine in Sheng Nong’s herbal classic, and in folk medicine it is used to treat rheumatoid arthritis (RA) ( JiangsuNew Medical College, 1986 ; Luo et al, 1993 ; Guan and Liu, 2002 ). For its further development, we established a process to prepare the diterpenoid fraction (DF) from R. molle fruit using resin and silica gel chromatography methods, and evaluated the antinociceptive activity, mechanism of action and toxicity of Rhodojaponin III, the main component of DF ( Yao et al, 2019 ; Yang et al, 2022 ). On the one hand, in vivo experiments indicated that DF had therapeutic effects on a collagen-induced arthritis (CIA) rat model and exerted analgesic and anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

The regulation of T helper cell polarization by the diterpenoid fraction of Rhododendron molle based on the JAK/STAT signaling pathway

Qin

Zheng

et al. 2022

Front. Pharmacol.

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The diterpenoid fraction (DF) prepared from fruit of Rhododendron molle was shown to have potential therapeutic effects on collagen-induced arthritis (CIA) rats based on our previous studies. As a continuation of those studies, herein, a lipopolysaccharide-induced endotoxin shock mouse model was used. The results showed that 0.2 mg/ml of DF significantly increased the mouse survival rate and had an anti-inflammatory effect. Further studies showed that DF could decrease the proportion of T helper cells (Th1 and Th17), and increase the proportion of Th2 and regulatory T cells (Tregs). Enzyme-linked immunosorbent assays indicated that DF inhibited the secretion of inflammatory cytokines such as TNF-α, IL-1β, and IL-6; western blotting showed that DF significantly reduced the levels of phosphorylated STAT1 and STAT3. In vitro, DF could dose-dependently inhibit the polarization of naive CD4+ T cells to Th1 or Th17 cells. DF at 10 μg/ml could markedly decrease the expression of mRNA encoding IFN-γ and T-bet, and suppress Th1 differentiation by downregulation of the activity of STAT1 and STAT4. Meanwhile, DF at 10 μg/ml remarkably reduced the expression of mRNA encoding IL-17a, IL-17f, and RORγt, and downregulated STAT3 phosphorylation, suggesting that DF could inhibit Th17 differentiation by reducing STAT3 activation. Taken together, DF blocked the JAK/STAT signaling pathway by inhibiting STAT1 and STAT3 phosphorylation, which clarified the important role of JAK/STAT signaling pathway in anti-rheumatoid arthritis.

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Evaluation of Rhodojaponin III from Rhododendron molle G. Don on oral antinociceptive activity, mechanism of action, and subacute toxicity in rodents

Cited by 9 publications

References 32 publications

Recent Advances in Grayanane Diterpenes: Isolation, Structural Diversity, and Bioactivities from Ericaceae Family (2018–2024)

Recent Advances in Grayanane Diterpenes: Isolation, Structural Diversity, and Bioactivities from Ericaceae Family (2018–2024)

Quantification of Rhodojaponin II and Rhodojaponin III in Rat Plasma by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry

The regulation of T helper cell polarization by the diterpenoid fraction of Rhododendron molle based on the JAK/STAT signaling pathway

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