Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron molle fruits

He, Yan-Chen; Yao, Yu-Min; Xue, Qiu-Wen; Fang, Xin; Liang, Shuang

doi:10.1016/s1875-5364(21)60019-5

Cited by 12 publications

(14 citation statements)

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“…Plant metabolites belonging to diverse chemical groups can exhibit different biological and pharmacological activities, e.g., antibacterial, antirheumatoid, antioxidant, anti-inflammatory, antinociceptive, enzyme inhibitory and cytotoxic potential [ 2 , 6 , 10 , 11 ]. Our previous research of Rhododendron luteum Sweet leaf extracts revealed the presence of active polyphenolic compounds.…”

Section: Resultsmentioning

confidence: 99%

“…The Rhododendron genus (Ericaceae family) comprises over 850 species distributed throughout the world, mainly in the northern hemisphere [ 1 ]. Rhododendrons produce secondary metabolites which exert various kinds of activity; many of them have been found to have low toxicity and to be effective in the treatment of chronic inflammation [ 2 ]. The main phytochemicals occurring in rhododendron species are polyphenols, especially flavonoids and terpenes [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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LC-ESI-MS/MS Characterization of Concentrated Polyphenolic Fractions from Rhododendron luteum and Their Anti-Inflammatory and Antioxidant Activities

2022

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The high biological potential of polyphenols encourages the search for new natural sources of and biomedical applications for these compounds. Rhododendron luteum Sweet was previously reported to contain pharmaceutically active polyphenols. The present research investigates the polyphenolic fractions in R. luteum leaves, including a determination of the free and bound phenolic acid and flavonoid contents and their anti-inflammatory and antioxidant activities. LC-ESI-MS/MS (liquid chromatography/electrospray ionization triple quadrupole mass spectrometry) analysis revealed a great abundance of free (e.g., 5-O-caffeoylquinic acid, ferulic acid, protocatechuic acid, catechin, and dihydromyricetin) and bound (e.g., caffeic acid, p-coumaric, protocatechuic acid, myricetin, quercetin) phenolics. The R. luteum samples exhibited high anti-inflammatory potential in lipoxygenase (IC50: 0.33 ± 0.01–2.96 ± 0.06 mg dry extract (DE)/mL) and hyaluronidase (IC50: 78.76 ± 2.09 – 429.07 ± 31.08 µg DE/mL) inhibition capacity assays. Some samples also had the ability to inhibit cyclooxygenase 1 (IC50: 311.8 ± 10.95 µg DE/mL) and cyclooxygenase 2 (IC50: 53.40 ± 5.07; 608.09 ± 14.78 µg DE/mL). All fractions showed excellent antioxidant activity in the Oxygen Radical Absorbance Capacity (ORAC) assay (5.76–221.81 g Trolox/g DE), ABTS•+ radical scavenging ability (0.62 ± 0.03 – 5.09 ± 0.23 g Trolox/g DE), and moderate ion (Fe2+) chelating power. This paper expands our knowledge of the phytochemistry and pharmacological activity of R. luteum polyphenols. It reveals, for the first time, the presence of dihydromyricetin, afzelin, and laricitrin in the plant material. It indicates biologically active polyphenolic fractions that should be further investigated or which could be efficiently used in pharmaceutical, cosmetic, or nutraceutical applications.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LC-ESI-MS/MS Characterization of Concentrated Polyphenolic Fractions from Rhododendron luteum and Their Anti-Inflammatory and Antioxidant Activities

2022

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“…After intragastric administration, RJ-III@HACC-SLNs showed a fast and durable effective analgesic effect in physical or chemically induced acute pain and chemically induced in ammatory pain, which may be attributed to the prolonged release of nanoparticles in vivo. The pro-in ammatory cytokines, including IL-1b, TNF-a, as well as IL-6 play an active role in pain [52][53][54], while according to the relevant studies, RJ-III exhibited a strong anti-in ammatory potential by suppressing pro-in ammatory cytokine levels (IL-1β, IL-6, and TNFα) [15]. Therefore, the anti-in ammatory effect of RJ-III might be the motive for its anti-nociceptive, subsequent experiments would be performed in antinociceptive mechanisms of RJ-III@HACC-SLNs.…”

Section: Acute Toxicitymentioning

confidence: 99%

“…For thousands of years, Rhododendron molle G. Don has been clinically used to treat pain in China [10]. Rhodojaponin III (RJ-III), a grayanane-type diterpenoid, of the natural products isolated from this herb, showed extensive biological activities [11][12][13] such as antinociceptive effects [14], anti-rheumatoid arthritis [15], lowering the blood pressure [16], slowing the heart rate [16], and inhibiting in ammatory response [17]. Remarkably, compared to morphine, RJ-III exhibited more e cacy in both acute as well as in ammatory pain models.…”

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confidence: 99%

Chitosan derivatives modified solid lipid nanoparticles prolonged Rhodojaponin-III active time and enhanced the safety and multimodal analgesic effects in vivo

Yang

Sun

et al. 2022

Preprint

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Background Rhodojaponin III (RJ-III), a bioactive diterpene, is a characteristic component of Rhododendron molle G. Don (Ericaceae), a potent analgesia in traditional Chinese medicine with thousands of years of clinical applications. However, its clinical use is limited by its acute toxicity and poor pharmacokinetic profile. To reduce such limitations, we incorporated RJ-III into the colloidal drug delivery system of hydroxypropyl trimethyl ammonium chloride chitosan (HACC) modified solid lipid nanoparticles (SLNs) to improve its sustained release and analgesic properties in vivo for oral delivery. Results The optimized RJ-III@HACC-SLNs were close to spherical, approximately 134 nm in size, with a positive zeta potential. In vitro experiments showed that RJ-III@HACC-SLNs were stable in the simulated gastric fluid, and were prolonged release in PBS (pH = 6.8). Pharmacokinetics results showed that after intragastric administration in mice, the relative bioavailability of RJ-III@HACC-SLNs was 87.9%, the peak time, half-time, and mean retention time of RJ-III@HACC-SLNs were significantly improved. Pharmacodynamic studies revealed that RJ-III@HACC-SLNs markedly reduced the acetic acid, hot, and formalin-induced nociceptive responses in mice (P < 0.001), and significantly increased the analgesic time (P < 0.01). Moreover, RJ-III@HACC-SLNs not only showed good biocompatibility with Caco-2 cells in vitro, but its LD50 value was also increased by 1.8-fold compared to RJ-III in vivo. Conclusions This study indicated that RJ-III@HACC-SLNs could exhibit certain toxicity-attenuating and effectiveness-enhancing effects by improving pharmacokinetic characteristics of the RJ-III, which could be a new strategy for intragastric delivery and analgesic treatment of RJ-III and HACC-modified SLNs, and provide a dosage form reference for the further study of RJ-III.

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“…For thousands of years, Rhododendron molle G. Don has been clinically used to treat pain in China. 10 Rhodojaponin III (RJ-III) is a grayanane-type diterpenoid isolated from the herb that shows extensive biological activities [11][12][13] such as antinociceptive effects, 14 anti-rheumatoid arthritis, 15 lowering the blood pressure, 16 slowing the heart rate, 16 and inhibiting inflammatory response. 17 Notably, RJ-III exhibits more efficacy as compared with morphine in both acute and inflammatory pain models.…”

Section: Introductionmentioning

confidence: 99%

Rhodojaponin III-Loaded Chitosan Derivatives-Modified Solid Lipid Nanoparticles for Multimodal Antinociceptive Effects in vivo

Yang¹,

Yang²,

Sun³

et al. 2022

IJN

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Background Rhodojaponin III (RJ-III) is a bioactive diterpenoid, which is mainly found in Rhododendron molle G. Don (Ericaceae), a potent analgesia in traditional Chinese medicine with several years of clinical applications in the country. However, its clinical use is limited by its acute toxicity and poor pharmacokinetic profiles. To reduce such limitations, the current study incorporated RJ-III into the colloidal drug delivery system of hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) to improve its sustained release and antinociceptive effects in vivo for oral delivery. Results The optimized RJ-III@HACC-SLNs were close to spherical, approximately 134 nm in size, and with a positive zeta potential. In vitro experiments showed that RJ-III@HACC-SLNs were stable in the simulated gastric fluid and had a prolonged release in PBS (pH = 6.8). Pharmacokinetic results showed that after intragastric administration in mice, the relative bioavailability of RJ-III@HACC-SLNs was 87.9%. Further, it was evident that the peak time, half-time, and mean retention time of RJ-III@HACC-SLNs were improved than RJ-III after the administration. In addition, pharmacodynamic studies revealed that RJ-III@HACC-SLNs markedly reduced the acetic acid, hot, and formalin-induced nociceptive responses in mice ( P < 0.001), and notably increased the analgesic time ( P < 0.01). Moreover, RJ-III@HACC-SLNs not only showed good biocompatibility with Caco-2 cells in vitro but its LD 50 value was also increased by 1.8-fold as compared with that of RJ-III in vivo. Conclusion These results demonstrated that RJ-III@HACC-SLNs improved the pharmacokinetic characteristics of the RJ-III, thereby exhibiting toxicity-attenuating potential and antinociceptive enhancing properties. Consequently, HACC-SLNs loaded with RJ-III could become a promising oral formulation for pain management that deserves further investigation in the future.

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Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron molle fruits

Cited by 12 publications

References 12 publications

LC-ESI-MS/MS Characterization of Concentrated Polyphenolic Fractions from Rhododendron luteum and Their Anti-Inflammatory and Antioxidant Activities

LC-ESI-MS/MS Characterization of Concentrated Polyphenolic Fractions from Rhododendron luteum and Their Anti-Inflammatory and Antioxidant Activities

Chitosan derivatives modified solid lipid nanoparticles prolonged Rhodojaponin-III active time and enhanced the safety and multimodal analgesic effects in vivo

Rhodojaponin III-Loaded Chitosan Derivatives-Modified Solid Lipid Nanoparticles for Multimodal Antinociceptive Effects in vivo

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