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Frontiers in Plant Science · 2022 · IF 6.627

Identification of alkaloids and related intermediates of Dendrobium officinale by solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry

Song Cheng,Zhang Yunpeng,Manzoor Muhammad Aamir,Li Guohui

Jasmonate (JA) signaling plays a pivotal role in plant stress responses and secondary metabolism. Many studies have demonstrated that JA effectively induce the expressions of alkaloid biosynthetic genes in various plants, which rendered to the accumulation of alkaloid to counteract stresses. Despite the multiple roles of JA in the regulation of plant growth and different stresses, less studied involved in the regulatory role of JA in Dendrobium officinale alkaloids. A strategy for the rapid identification of alkaloid and the intermediates of D. officinale was established based on a solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry method. By using SPE-LC-MS/MS method, the potential compounds were tentatively identified by aligning the accurate molecular weight with the METLIN and Dictionary of Natural Products databases. The chemical structures and main characteristic fragments of the potential compounds were further confirmed by retrieving the multistage mass spectra from the MassBank and METLIN databases. The Mass Frontier software was used to speculate the fragmentation pathway of the identified compounds. Seven alkaloids were separated and identified from D. officinale, which were mainly classified into five types (tropane alkaloids, tetrahydroisoquinoline alkaloids, quinolizidine alkaloids, piperidine alkaloids, and spermidine alkaloids). Besides the alkaloids, forty-nine chemical substances, including guanidines, nucleotides, dipeptides, sphingolipids and nitrogen-containing glucosides, were concurrently identified. These findings gives the composition of chemicals currently found in D. officinale, which could provide the scientific method for the identification of alkaloids in other Dendrobium plants.

CAS / MDL: 50-55-5
研究领域: 植物化学 · 药用植物学 · 代谢组学
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PROCESS BIOCHEMISTRY · 2023 · IF 4.4

Ultrasound and deep eutectic solvent as green extraction technology for recovery of phenolic compounds from Dendrobium officinale leaves

Peiyi Wang,Baoming Tian,Zhiwei Ge,Jicai Feng,Jian Wang,Kai Yang,Peilong Sun,Ming Cai

Ultrasound and deep eutectic solvent (DES) are two green and efficient techniques in extraction. In this study, an eco-friendly extraction of phenolic compounds from Dendrobium officinale leaves (DOLs) was investigated. Ten DESs containing choline chloride, betaine , organic acids, polyols and amide, were tailored for extraction. Choline chloride-oxalic acid showed the most promising efficiencies for phenolics as 9.84 ± 0.19 mg GAE/g DW. Ultrasound-assisted DES (UADES) were optimized by a Box-Behnken design of response surface methodology. The optimum conditions were ultrasonic power 330 W, extraction temperature 60 ℃, and liquid-solid ratio 53:1 mL/g with a total phenolic content (TPC) of 17.50 ± 0.35 mg GAE/g DW. Compared with a single or triple frequency ultrasound, a dual-frequency of 40/60 kHz treatment for 15 min made TPC up to be 25.15 ± 1.46 mg GAE/g DW. About 13 phenolics were identified by UPLC-Triple-TOF/MS as the crucial phenolics in extracts , such as rutin and apigenin flavonoids . In addition, leave surface changed dramatically by UADES. These phenolic extracts had eminent antioxidant capacities, such as DPPH• scavenging rate of 65.4% and FRAP value of 0.234 mmol/L FeSO 4 at TPC of 4 mg/mL. Accordingly, dual-frequency UADES is a meaningful and green technology for extraction of phenolic compounds.

研究领域: 植物化学 · 天然产物开发 · 食品科学
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PHYTOMEDICINE · 2022 · IF 6.656

Dendrobine inhibits dopaminergic neuron apoptosis via MANF-mediated ER stress suppression in MPTP/MPP+-induced Parkinson's disease models

Qiang-Ming Li,Xiang Li,Shuang-Qiao Su,Yu-Tong Wang,Tong Xu,Xue-Qiang Zha,Li-Hua Pan,Zhen-Zi Shang,Feng-Yun Zhang,Jian-Ping Luo

Background Parkinson's disease (PD) is an age-related neurodegenerative disorder without effective treatments. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been suggested to be capable of protecting against PD by inhibiting endoplasmic reticulum (ER) stress-mediated neuronal apoptosis. Purpose This study was aimed to evaluate the antiparkinsonian effect of dendrobine and reveal its underlying mechanisms from the perspective of MANF-mediated ER stress suppression. Methods Behavioral assessments of PD mice as well as LDH/CCK-8 assay in SH-SY5Y cells and primary midbrain neurons were carried out to detect the antiparkinsonian effect of dendrobine. Immunofluorescence, western blot, flow cytometry and shRNA-mediated MANF knockdown were used to determine the apoptosis of dopaminergic neurons and the expressions of ER stress-related proteins for investigating the underlying mechanism of dendrobine. Results Dendrobine significantly ameliorated the motor performance of PD mice and attenuated the injuries of dopaminergic neurons. Dendrobine could also relieve neuronal apoptosis, up-regulate MANF expression and inhibit ER stress, which were largely abolished by shRNA-mediated MANF knockdown in PD model. Conclusion Dendrobine might protect against PD by inhibiting dopaminergic neuron apoptosis, which was achieved by facilitating MANF-mediated ER stress suppression. Our study suggested that dendrobine could act as a MANF up-regulator to protect against PD, and provided a potential candidate for exploring etiological agents of PD.

CAS / MDL: 59-92-7 28289-54-5
研究领域: 神经科学 · 药理学 · 分子生物学
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PHYTOMEDICINE · 2026 · IF 11.3

Dendrobine ameliorates diabetic cardiomyopathy by targeting KEAP1 to disrupt KEAP1-NRF2 interaction and activate antioxidant defense

Xiaojue Xiang,Xu Lin,Qifang Wu,Xiaoming Zhang,Xueliang Fu,Linya Wu,Haibin Tong,Zhenyu Dai

Dendrobium officinale extract DOE ameliorates metabolic disorders and diabetic cardiomyopathy. • DOE reduced myocardial injury, fibrosis, and oxidative stress via activating NRF2 pathway. • Dendrobine was the principal cardioprotective alkaloid in DOE against diabetic cardiomyopathy . • Dendrobine directly targets KEAP1 Kelch domain to disrupt the KEAP1-NRF2 interaction . Background Dendrobium officinale Kimura et Migo is a prestigious traditional Chinese medicine historically used for treating "Xiao-Ke" (diabetes and its complications). However, the specific material basis and direct molecular targets responsible for its efficacy against diabetic cardiomyopathy (DCM) remain largely obscure. This study aimed to systematically investigate whether dendrobine, the characteristic active alkaloid of DO, serves as the principal cardioprotective component by directly targeting the KEAP1-NRF2 signaling axis. Methods The therapeutic effects of D. officinale extract (DOE) and dendrobine were evaluated in vivo using db/db mice and in vitro using high-glucose (HG)-challenged H9c2 cardiomyocytes. Cardiac pathological remodeling, lipid peroxidation, and systemic metabolic profiles were comprehensively assessed. The direct interaction between dendrobine and KEAP1 was definitively characterized using Co-Immunoprecipitation (Co-IP), Cellular Thermal Shift Assay (CETSA), Drug Affinity Responsive Target Stability (DARTS), MicroScale Thermophoresis (MST), and 100-ns Molecular Dynamics (MD) simulations. Reverse pharmacological validation was performed using NRF2-specific siRNA and the inhibitor ML385. Results In vivo , DOE significantly ameliorated systemic insulin resistance, hyperlipidemia, and myocardial pathological remodeling in db/db mice while robustly suppressing myocardial oxidative stress (MDA, 4-HNE) by upregulating NRF2-driven antioxidant enzymes (HO-1, NQO1, GPX4). In vitro , dendrobine dose-dependently replicated these cardioprotective and antioxidative efficacies. Mechanistically, dendrobine promoted NRF2 nuclear translocation and initiated the downstream antioxidant cascade. Crucially, MST and CETSA revealed that dendrobine binds directly to KEAP1 with high affinity ( K d  = 1.18 μM), functioning as a competitive protein-protein interaction (PPI) inhibitor to disrupt the KEAP1-NRF2 complex. MD simulations and mutagenesis validation pinpointed the Kelch domain of KEAP1 (specifically residue Arg415) as the binding pocket. Finally, silencing or inhibiting NRF2 abolished the anti-hypertrophic and cytoprotective effects of dendrobine, and the in vivo administration of dendrobine successfully recapitulated the metabolic regulation and KEAP1/NRF2-mediated cardioprotection of DOE in db/db mice. Conclusion Dendrobine, the principal alkaloid of D. officinale , effectively ameliorates diabetic cardiomyopathy by functioning as a novel, direct competitive inhibitor of the KEAP1-NRF2 interaction. This targeted disruption liberates NRF2 to restore myocardial redox homeostasis, highlighting dendrobine as a promising lead compound for DCM therapy. Download: Download high-res image (395KB) Download: Download full-size image

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Drug Design Development and Therapy · 2025 · IF 5.1

Shatai Heji Mitigates Sjögren Disease-Induced Xerostomia by Regulating AQP5, NF-κB, and p38 MAPK Signaling Pathwaysaff

Fangbin Liu,Jiyuan Chen,Chunai Gong,Minyan Chen,Gang Yang,Chun Chen,Ru Yao,Shengnan Li,Rong Wang,Yongfang Yuan

Introduction Xerostomia, commonly caused by Sjögren disease (SjD) or head and neck radiotherapy, significantly impairs patients’ quality of life, yet effective treatments remain limited. Traditional Chinese Medicine (TCM) offers promising alternatives due to its favourable efficacy and low toxicity. Shatai Heji (STHJ), a compound TCM formulation designed to nourish yin and invigorate qi, shows therapeutic potential for xerostomia. This study aimed to establish quality control standards for STHJ and evaluate its pharmacodynamics, safety, and mechanisms of action in models of xerostomia.Methods A qualitative identification method was developed for the twelve herbal components of STHJ, with quantification of active constituents, focusing on quality markers for Astragalus and Rehmannia. Xerostomia was induced in Sprague–Dawley (SD) rats using a muscarinic receptor antagonist, and in BALB/c mice with SjD. Histological examination of major organs and salivary glands was performed, and aquaporin-5 (AQP5) expression in submandibular glands was assessed via Western blotting and immunohistochemistry. Therapeutic effects were evaluated through salivary secretion, glandular weight, and biochemical markers. In SjD mice, submandibular gland immunofluorescence and ELISA were used to assess inflammatory cytokines (TNF-α, TNF-β, IFN-γ, IL-6) and autoantibodies (anti-SSA/Ro, anti-SSB/La). Western blotting was used to analyse NF-κB and MAPK p38 pathway activation. Acute toxicity was assessed in SD rats.Results STHJ significantly improved xerostomia symptoms, increased salivary output, upregulated AQP5, and preserved glandular morphology. It reduced fibrosis, suppressed inflammatory cytokine expression, and inhibited immune cell infiltration. Mechanistically, STHJ attenuated activation of NF-κB and MAPK p38 pathways. No acute toxicity was observed.Conclusion This is the first study to establish quality control standards for STHJ and to demonstrate its anti-inflammatory and immunomodulatory effects in xerostomia models. The findings suggest that STHJ may serve as a safe and effective therapeutic option for xerostomia associated with SjD and other conditions.

CAS / MDL: 2115-91-5
研究领域: 药理学 · 免疫学 · 中医中药 · 分子生物学 · 风湿病学
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