Neuroprotection of Andrographolide Against Microglia-Mediated Inflammatory Injury and Oxidative Damage in PC12 Neurons

Xu, Yuanzhen; Tang, Dan; Wang, Jianping; Wei, Hongbo; Gao, Jin‐Ming

doi:10.1007/s11064-019-02883-5

Cited by 46 publications

(30 citation statements)

References 35 publications

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“…According to previously reported methods [30,31], we used rat pheochromocytoma PC12 cells as a model system of neuronal differentiation to measure the effects of the synthesized compounds hamigeran B (2), 9a-n and 9o-w on neurite outgrowth, with NGF (10 ng/mL) as positive control. Specifically, as shown in Figure 3, most of them in combination with NGF (10 ng/mL) showed NGFmediated neurite-outgrowth promoting activities, and 9a, 9h, 9o, and 9q exhibited significant methods [32,33]. The results of inhibitory effects are depicted in Figure 4.…”

Section: Biological Evaluationmentioning

confidence: 93%

“…The most important thing is that they can be cheaply stored and transported as the less deliquescent than quercetin. The inhibitory effects of the hamigeran B derivatives (9a-n) and 1-hydroxyl-9-epi-hamigeran B ones (9o-w) on LPS-stimulated NO production in BV2 cells were assessed according to our reported methods [32,33]. The results of inhibitory effects are depicted in Figure 4.…”

Section: Biological Evaluationmentioning

confidence: 99%

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Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators

Han

et al. 2020

Marine Drugs

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We describe the efficient synthesis of a series of new simplified hamigeran B and 1-hydroxy-9-epi-hamigeran B norditerpenoid analogs (23 new members in all), structurally related to cyathane diterpenoid scaffold, and their anti-neuroinflammatory and neurite outgrowth-stimulating (neurotrophic) activity. Compounds 9a, 9h, 9o, and 9q exhibited moderate nerve growth factor (NGF)-mediated neurite-outgrowth promoting effects in PC-12 cells at the concentration of 20 μm. Compounds 9b, 9c, 9o, 9q, and 9t showed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, of which 9c and 9q were the most potent inhibitors, with IC50 values of 5.85 and 6.31 μm, respectively. Two derivatives 9q and 9o as bifunctional agents displayed good activities as NO production inhibitors and neurite outgrowth-inducers. Cytotoxicity experiments, H2O2-induced oxidative injury assay, and ELISA reaction speculated that compounds may inhibit the TNF-α pathway to achieve anti-inflammatory effects on nerve cells. Moreover, molecular docking studies provided a better understanding of the key structural features affecting the anti-neuroinflammatory activity and displayed significant binding interactions of some derivatives (like 9c, 9q) with the active site of iNOS protein. The structure-activity relationships (SARs) were also discussed. These results demonstrated that this structural class compounds offered an opportunity for the development of a new class of NO inhibitors and NGF-like promotors.

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Section: Biological Evaluationmentioning

confidence: 93%

Section: Biological Evaluationmentioning

confidence: 99%

Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators

Han

et al. 2020

Marine Drugs

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“…A concentration of 1 µM (0.35 µg/mL) in plasma is obtained within 30 min after administration of 50 mg/kg and bioavailability is 1.19% [25]. Andrographolide was measured in plasma and various rat Several data have reported the antioxidant activities of andrographolide in various in vitro and in vivo model systems [22,23]. This review describes its pharmacokinetic parameters and examines the current status regarding the antioxidant effect of andrographolide.…”

Section: Andrographolide Bioavailabilitymentioning

confidence: 99%

“…Many studies have focused on the anti-viral [12][13][14], anti-thrombotic [15,16], hepatoprotective [17,18], anticancer [19,20], and anti-inflammatory properties [21] of andrographolide. Several data have reported the antioxidant activities of andrographolide in various in vitro and in vivo model systems [22,23]. This review describes its pharmacokinetic parameters and examines the current status regarding the antioxidant effect of andrographolide.…”

Section: Introductionmentioning

confidence: 99%

Andrographolide, A Natural Antioxidant: An Update

et al. 2019

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Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

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“…It is referred to as "Indian Echinacea" by Strong [25]. The plant was evaluated for its various medicinal properties over the years such as anti-cancer [26][27][28], anti-viral [29,30], cardio protecting [31], and neuro-protectant [32]. A. paniculata is one of the main ingredients in pain killer and anti-inflammatory drugs, e.g., ParActin and ArmaForce.…”

Section: Introductionmentioning

confidence: 99%

Molecular Cloning and Differential Gene Expression Analysis of 1-Deoxy-D-xylulose 5-Phosphate Synthase (DXS) in Andrographis paniculata (Burm. f) Nees

et al. 2020

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Andrographis paniculata 1-deoxy-D-xylulose-5-phosphate synthase (ApDXS) gene (GenBank Accession No MG271749.1) was isolated and cloned from leaves for the first time. Expression of ApDXS gene was carried out in Escherichia coli Rosetta cells. Tissue-specific ApDXS gene expression by quantitative RT-PCR (qRT-PCR) revealed maximum fold expression in the leaves followed by stem and roots. Further, the differential gene expression profile of Jasmonic acid (JA)-elicited in vitro adventitious root cultures showed enhanced ApDXS expression compared to untreated control cultures. A. paniculata 3-hydroxy-3-methylglutaryl-coenzyme A reductase (ApHMGR) gene expression was also studied where it was up-regulated by JA elicitation but showed lower expression compared to ApDXS. The highest expression of both genes was found at 25 µm JA elicitation followed by 50 µm. HPLC data indicated that the transcription levels were correlated with increased andrographolide accumulation. The peak level of andrographolide accumulation was recorded at 25 μM JA (9.38-fold) followed by 50 µM JA (7.58-fold) in elicitation treatments. The in silico generated ApDXS 3D model revealed 98% expected amino acid residues in the favored and 2% in the allowed regions of the Ramachandran plot with 92% structural reliability. Further, prediction of conserved domains and essential amino acids [Arg (249, 252, 255), Asn (307) and Ser (247)] involved in ligand/ inhibitor binding was carried out by in silico docking studies. Our present findings will generate genomic information and provide a blueprint for future studies of ApDXS and its role in diterpenoid biosynthesis in A. paniculata.

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Neuroprotection of Andrographolide Against Microglia-Mediated Inflammatory Injury and Oxidative Damage in PC12 Neurons

Cited by 46 publications

References 35 publications

Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators

Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators

Andrographolide, A Natural Antioxidant: An Update

Molecular Cloning and Differential Gene Expression Analysis of 1-Deoxy-D-xylulose 5-Phosphate Synthase (DXS) in Andrographis paniculata (Burm. f) Nees

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