Three herbal extracts protect mitochondrial function in a cellular model of Parkinson’s disease
“Mitochondrial dysfunction is strongly associated with PD pathogenesis.”
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image:
Figure 6. Protective effects of herbal extracts on TPA-differentiated dopaminergic SH-SY5Y cells with VPS13C knockdown. In brief, SH-SY5Y cells were differentiated using TPA, infected with lentiviral shRNA, and treated with the herbal extracts. (A) Cell protein (VPS13C, SOD1, SOD2, NRF2, PGC-1α, BCL2, and BAX) expression, (B) MMP, (C) mitochondrial O2●− content (MitoSOX staining; red), (D) mitochondrial mass (NAO staining; green), and (E) mtDNA content (qPCR) were measured on day 8 (n = 3). For normalization, the relative levels of VPS13C, SOD1, SOD2, NRF2, PGC-1α, BCL2, BAX, mitochondrial O2●−, mitochondrial mass, and mtDNA in scrambled shRNA-infected cells were set to 100%. Cell nuclei were counterstained with (C) DAPI or (D) Hoechst 33342 (blue). Data, presented as means ± SDs, were analyzed using one-way ANOVA, followed by Tukey’s post hoc test; #p < 0.05, ##p < 0.01, and ###p < 0.001, compared with scrambled shRNA-treated cells, or *p < 0.05, **p < 0.01, and ***p < 0.001, compared with cells not treated with any herbal extract.
view moreCredit: Copyright: © 2026 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
BUFFALO, NY — September 9, 2026 — A new research paper was published in Volume 18 of Aging on August 13, 2026, titled “Protective effects of three herbal extracts on mitochondrial dysfunction in VPS13C-knockdown SH-SY5Y cells: implications for Parkinson’s disease.”
The study was led by co-first authors Yih-Ru Wu and Chih-Hsin Lin from the Chang Gung Memorial Hospital, Chang Gung University College of Medicine in Taoyuan, Taiwan, and Pei-Syuan Huang from the School of Life Science at National Taiwan Normal University in Taipei, Taiwan. Corresponding authors I-Cheng Chen and Guey-Jen Lee-Chen are from the School of Life Science at National Taiwan Normal University. The paper identifies Wu, Lin, and Huang as equal contributors.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized primarily by dysfunction and loss of dopaminergic neurons in the substantia nigra. Although its causes are complex, mitochondrial dysfunction and oxidative stress are important biological processes implicated in both sporadic and inherited forms of the disease. The researchers focused on VPS13C, also known as PARK23, a gene associated with a rare autosomal recessive form of early-onset parkinsonism. Loss of VPS13C function has previously been linked to impaired mitochondrial function.
The study investigated three extracts used in traditional Chinese medicine: Uncaria rhynchophylla (UR), Gardenia jasminoides (GJ), and Scutellaria baicalensis (SB). Previous experimental studies have reported neuroprotective effects from these plants or their bioactive constituents in models relevant to PD. The researchers examined whether the extracts could protect cells against mitochondrial dysfunction associated with reduced VPS13C expression.
Chemical analyses identified several potentially bioactive constituents in the extracts. UR contained rhynchophylline and isorhynchophylline; GJ contained geniposide and crocin; and SB contained several flavonoids, including baicalin, wogonoside, baicalein, wogonin, and oroxylin A. Across the concentrations initially tested, the three extracts maintained greater than 90% viability in SH-SY5Y cells after 24 hours, indicating low cytotoxicity under these experimental conditions.
The researchers first created a chemical model of mitochondrial stress using carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), which uncouples mitochondrial oxidative phosphorylation. FCCP treatment reduced cell viability and mitochondrial membrane potential while markedly increasing mitochondrial superoxide production. Pretreatment with UR, GJ, or SB partially counteracted these effects. At selected concentrations, the extracts improved cell viability and mitochondrial membrane potential, reduced mitochondrial superoxide, and increased mitochondrial mass and mitochondrial DNA content.
The researchers then developed a genetic model by using lentiviral short hairpin RNA to reduce VPS13C expression in human SH-SY5Y neuroblastoma cells. Combined targeting of the 3′ and 5′ regions of VPS13C reduced its mRNA expression to approximately 29% of control levels. This was accompanied by reduced cell viability and mitochondrial membrane potential and an almost threefold increase in mitochondrial superoxide production, providing a cellular system for examining the protective effects of the extracts.
For experiments more closely modeling neuronal characteristics, SH-SY5Y cells were differentiated into dopaminergic-like cells and then subjected to VPS13C knockdown. Treatment with each herbal extract increased VPS13C expression and reduced several indicators of cellular injury. The extracts decreased lactate dehydrogenase release, caspase-3 activity, and reactive oxygen species production while improving neurite length, process number, and branching.
The researchers also observed changes in proteins involved in antioxidant defense, mitochondrial regulation, and apoptosis. VPS13C knockdown reduced SOD1, SOD2, NRF2, PGC-1α, and the anti-apoptotic protein BCL2 while increasing the pro-apoptotic protein BAX. Treatment with the three herbal extracts significantly reversed these changes. The extracts also increased mitochondrial membrane potential and mitochondrial mass while reducing mitochondrial superoxide production.
“Depletion of VPS13C leads to mitochondrial dysfunction.”
These results suggest several possible mechanisms underlying the observed cellular protection. Increased SOD1 and SOD2 may strengthen antioxidant defenses, while NRF2 and PGC-1α are involved in responses to oxidative stress and regulation of mitochondrial function and biogenesis. Changes in BCL2 and BAX are also consistent with reduced susceptibility to apoptotic cell death. The authors discuss isorhynchophylline in UR, geniposide in GJ, and baicalein in SB as compounds that may contribute to the protective effects, based partly on evidence from previous experimental studies.
Importantly, the findings are preclinical and do not demonstrate that these herbal extracts can prevent or treat Parkinson’s disease in people. The experiments were performed in an immortalized human neuroblastoma cell line, which cannot reproduce the complex three-dimensional environment of the human brain, interactions between neurons and glial cells, or systemic pharmacokinetics. Although no cytotoxicity was observed in the SH-SY5Y cells under the tested conditions, effects on other brain cell types remain unknown. The authors therefore call for further studies using primary neuronal cultures, human induced pluripotent stem cell-derived dopaminergic neurons, animal models, and other complementary systems.
Overall, the study provides cellular evidence that Uncaria rhynchophylla, Gardenia jasminoides, and Scutellaria baicalensis extracts can reduce oxidative stress and mitochondrial dysfunction associated with VPS13C depletion. By improving mitochondrial measures, antioxidant defenses, cell-survival signaling, and neurite growth in VPS13C-knockdown SH-SY5Y cells, the findings support further investigation of these extracts and their active compounds as potential candidates for Parkinson’s disease research. However, substantial additional preclinical validation will be required before their therapeutic relevance in patients can be determined.
Paper DOI: https://doi.org/10.18632/aging.206409
Corresponding authors: I-Cheng Chen ichen@ntnu.edu.tw, Guey-Jen Lee-Chen t43019@ntnu.edu.tw
Abstract video: https://www.youtube.com/watch?v=kM8hO89d_9k
Keywords: aging, Parkinson’s disease, traditional Chinese medicine, VPS13C knockdown, mitochondrial dysfunction, oxidative stress
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Aging-US
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Article Title
Protective effects of three herbal extracts on mitochondrial dysfunction in VPS13C-knockdown SH-SY5Y cells: implications for Parkinson’s disease
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