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Protocatechualdehyde
REPRODUCTIVE TOXICOLOGY · 2025 · IF 2.8

Protocatechualdehyde improves cyclophosphamide-induced premature ovarian insufficiency by inhibiting granulosa cell apoptosis and senescence through the SIRT1/p53 axis

Cong Feng,Yue Jiang,Yi Wang,Yuehui Zhang,Yu Liu,Jia Li

Premature ovarian insufficiency (POI) is a prevalent gynecological disorder. Cyclophosphamide (CP), as a chemotherapeutic drug, particularly plays an important role in inducing POI. Protocatechualdehyde (PCA) is a major phenolic acid in Chinese herb Danshen, and has been reported to have beneficial effects on anti-inflammatory, anti-apoptotic, and anti-oxidant functions. We aimed to investigate the effect of different doses of PCA on ovarian function and the underlying molecular mechanisms. PCA administration reduced estrous cycle disorders, increased ovarian weight, promoted the secretion of serum hormone levels, and improved the CP-damaged ovarian microenvironment. Importantly, the administration of PCA contributed to the recovery of ovarian function with POI by inhibiting the senescence and apoptosis of granulosa cells. In vitro assay further confirmed the protective effect of PCA on CP-induced senescence and apoptosis of granulosa cells. Mechanistically, both in vivo and in vitro experiments proved that PCA administration promoted activation of the Sirt1/p53 signaling cascade, ultimately improving ovarian function. In conclusion, PCA might protect against ovarian damage in CP-induced POI that might be related to its activity on senescence and apoptosis of granulosa cells by the Sirt1/p53 pathway.

CAS / MDL: 28718-90-3
研究领域: 生殖医学 · 药理学 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Molecular insights into the anti-browning effect of protocatechualdehyde

Yan-Ping Lin,Dong-Yan Zhou,Shang-Guang Du,Zi-Fan Yu,Rui-Na Zhou,Hao-Miao Li,Wei-Ming Chai

Protocatechualdehyde (PCA) is a better PPO inhibitor than ellagic acid. • PCA causes structural stretching and conformational change of PPO. • PCA is demonstrated as a potent anti-browning agent. • PCA regulates phenolic metabolism, reduces lipid peroxidation, boosts AsA-GSH cycle. • PCA regulates cell wall metabolism, inhibiting senescence-related browning. Polyphenol oxidase (PPO) is a vital polyphenol-metabolizing enzyme responsible for the enzymatic browning of fruits and vegetables. This study assessed the anti-PPO activity of protocatechualdehyde (PCA), yielding an IC 50 value of 94 μM (95% CI: 91.8 to 96.4 μM). Kinetic analysis revealed that PCA acted as a reversible and competitive inhibitor of PPO. Molecular docking indicated that hydrogen bonding and hydrophobic interactions were the main driving forces for PCA-PPO binding. Fluorescence spectroscopy further demonstrated that PCA binding altered the microenvironments around tyrosine and tryptophan residues, leading to conformational rearrangements and partial unfolding of the enzyme, evidenced by significant fluorescence quenching. Molecular dynamics simulation demonstrated that PCA perturbed the secondary structure of PPO and caused stretching of its overall structure, thereby inhibiting the catalytic activity of the enzyme. Furthermore, PCA demonstrated excellent anti-browning activity by regulating phenolic metabolism, reducing membrane lipid peroxidation, enhancing the ascorbic acid-glutathione cycle, and modulating cell wall metabolism to delay cellular senescence. Collectively, these findings offer some valuable insights into the development of PPO inhibitor and anti-browning agent, and provide a theoretical foundation for the potential application of PCA in the area of food preservation. Download: Download high-res image (249KB) Download: Download full-size image

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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2017 · IF 2.323

Thermodynamic Difference between Protocatechualdehyde and p-Hydroxybenzaldehyde in Aqueous Sodium Chloride Solutions

Jimin Xie,Min Liu,Guiqin Liu,Lixia Yuan,Dacheng Li,Zhiping Fan,Zhengping Wang,Bingquan Wang,Jun Han

The enthalpies of dilution of protocatechualdehyde and p-hydroxybenzaldehyde in the aqueous sodium chloride solutions were measured by using a mixing-flow microcalorimeter at 298.15 K. Densities of the ternary homogeneous systems at different temperatures (293.15, 298.15, 303.15, 308.15, and 313.15 K) were also measured with a quartz vibrating-tube densimeter. The homogeneous enthalpic interaction coefficients (h2, h3, and h4) were calculated according to the excess enthalpy concept based on the calorimetric data. The apparent molar volumes (Vϕ) and standard partial molar volumes (Vϕ0) of the investigated system were computed from their density data. The variation trends in h2 and Vϕ0 with increasing salt molality were obtained and discussed in terms of the (solute + solute) and (solute + solvent) interactions. The experimental results showed that the molecular structures of protocatechualdehyde and p-hydroxybenzaldehyde, especially the number of hydroxyl groups, have evident influence on their thermodynamic properties. The thermodynamic data obtained in this work may be helpful for exploring the structure–function relationship of protocatechualdehyde and p-hydroxybenzaldehyde.

CAS / MDL: 7647-14-5
研究领域: 物理化学 · 药物化学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Multifunctional Antiswelling Hydrogel for Underwater Sensing Achieved through Ultrafast Protocatechualdehyde-Fe3+ Autocatalytic Gelation

Chunyue Zhao,Jinfeng Xing

Hydrogel-based sensors typically exhibit pronounced swelling underwater, leading to the accelerated deterioration of mechanical properties and signal distortion, thereby limiting their applicability. In this study, we developed an antiswelling hydrogel comprising N, N′-methylenebis (acrylamide)-cross-linked poly(acrylic acid) (PAAc) and polylysine (PLL) in a water/glycerol (Gl) binary solvent system via a protocatechualdehyde (PA)-Fe3+ autocatalytic system, inspired by natural catechol/metal-ion coordination and solvent-exchange strategies. The PA-Fe3+ system rapidly initiates AAc polymerization at ambient temperature, while Gl’s viscosity regulates heat transfer and enhances reaction efficiency. Upon underwater immersion, Gl is replaced with water molecules, triggering network reconstruction through ion complexation and electrostatic interactions to form a dense spatial structure. The antiswelling performance is tunable by adjusting PA/Fe3+ ratios and Gl content. Remarkably, the hydrogel maintains stable mechanical properties and sensing functions in both air and underwater environments. It enables both airborne motion sensing (e.g., speech recognition) and underwater strain sensing (e.g., Morse code detection). This study provides a facile strategy for the design of conductive hydrogel sensors with antiswelling performance for long-term underwater applications.

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Frontiers in Pharmacology · 2026 · IF 5.4

Protocatechualdehyde ameliorates OGD/R-induced endothelial injury via the ROS/miR-29b-3p/SIRT1 regulatory axis

Yanqing Wu,Xilin Qiao,Shuaiyu Chen,Yalan Lu,Bingyan Mao,Mengdie Zhu,Xinzhi Chen,Nipi Chen,Zhishan Ding,Bo Jin

Introduction MicroRNA-29b-3p (miR-29b-3p) plays a critical role in regulating endothelial apoptosis and autophagy. We previously demonstrated that protocatechualdehyde (PCA), a water-soluble phenolic acid derived from Salvia miltiorrhiza Bge., protects human umbilical vein endothelial cells (HUVECs) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury. However, whether miR-29b-3p mediates this protective effect remains unclear. Methods Using the OGD/R in vitro model of ischemia-reperfusion injury, we investigated the molecular mechanisms underlying ischemic damage at the cellular level. RT-qPCR was used to measure miR-29b-3p expression, Western blotting to assess autophagy- and apoptosis-related proteins, and MDC staining and flow cytometry to evaluate autophagy and apoptosis, respectively. Results The results showed that miR-29b-3p was downregulated in OGD/R-treated HUVECs, an effect that was reversed by PCA and the ROS inhibitor N-acetylcysteine (NAC). The miR-29b-3p mimic enhanced the promoting effects of PCA and NAC on miR-29b-3p expression, whereas miR-29b-3p inhibitor reversed these effects. Similarly, PCA-induced autophagy and inhibition of apoptosis were enhanced by the miR-29b-3p mimic and reversed by the inhibitor. To determine whether SIRT1 acts downstream of miR-29b-3p, we used EX527 (a SIRT1 inhibitor) and found that it attenuated the PCA-mediated upregulation of miR-29b-3p. The miR-29b-3p mimic enhanced PCA-induced SIRT1 activity and protein expression, while the inhibitor had the opposite effect. Additional experiments revealed that NAC suppressed ROS by upregulating miR-29b-3p, leading to increased SIRT1 expression and reduced apoptosis. Disscussion Collectively, these findings demonstrate that PCA ameliorates OGD/R-induced endothelial injury by promoting autophagy and inhibiting apoptosis via the ROS/miR-29b-3p/SIRT1 regulatory axis.

CAS / MDL: 501-98-4
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Antioxidant and antibacterial hydrogel formed by protocatechualdehyde–ferric iron complex and aminopolysaccharide for infected wound healing

Jianbin Deng,Shiqi Gao,Mengqi Liu,Weiquan Xie,Guang-Yu Pan

To better treat bacteria-infected wounds and promote healing, new wound dressings must be developed. In this study, we obtained PA@Fe by chelating iron trivalent ions (Fe 3+ ) with protocatechualdehyde (PA), which has a catechol structure. Subsequently, we reacted it with ethylene glycol chitosan (GC) via a Schiff base reaction and loaded vancomycin to obtain an antibacterial Gel@Van hydrogel with a photothermal response. The as-prepared Gel@Van hydrogel exhibited good injectability, self-healing, hemostasis, photothermal stability, biocompatibility, and antioxidant and antibacterial properties. Moreover, Gel@Van hydrogel achieved highly synergistic antibacterial efficacy through photothermal and antibiotic sterilization. In a mouse skin-damaged infection model, Gel@Van hydrogel had a strong ability to promote the healing of methicillin-resistant Staphylococcus aureus ( MRSA )-infected wounds, indicating the great potential application value of Gel@Van hydrogel in the field of treating and promoting the healing of infected wounds.

研究领域: 材料科学 · 生物医学工程 · 伤口护理 · 药剂学
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Frontiers in Microbiology · 2024 · IF 4

Antibacterial and antibiofilm activities of protocatechualdehyde and its synergy with ampicillin against methicillin-resistant Staphylococcus aureus

Wang Ying,Song Lin,Chen Kun,Shi Chao,Peng Chuantao,Yang Qingli,Li Zhaojie

Protocatechualdehyde (PA) is a phenolic acid present in many plants and has many biological activities. Herein, the antagonistic effects and the action mechanism of PA against methicillin-resistant Staphylococcus aureus (MRSA) were studied. The results showed that PA had both significant antibacterial and anti-biofilm activities against MRSA. Additionally, PA had synergy with ampicillin against MRSA. It was elucidated that PA was prominent in destroying cell membranes, increasing cell membrane permeability and intracellular ROS production, thus leading to bacterial cell damage. Transcriptome analysis showed that PA disrupts many physiological pathways, including increasing cell membrane permeability, inhibiting biofilm formation, decreasing resistance to antimicrobial agents, and impairing DNA replication. Finally, the antimicrobial preservation test showed that PA could inhibit the growth of MRSA and prevent the corruption of beef. In summary, PA is an effective natural antibacterial substance and has a good application potential in food preservation, even in tackling antibiotic resistance problems.

CAS / MDL: 139-85-5
研究领域: 微生物学 · 药理学 · 食品科学 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Multifunctional sericin-protocatechualdehyde‑silver sulfadiazine bioactive hydrogel with dual antibacterial and antioxidant activities for managing chronic wounds

Qian Huang,Zhanyan Du,Wengong Huang,Gang Xu,Limin Bai,Xitao Cao,Guozheng Zhang,Yeshun Zhang

Chronic wounds represent a significant clinical challenge, as bacterial infection and oxidative stress synergistically impede the healing process. There is a pressing need for multifunctional dressings that can concurrently eradicate pathogens and alleviate oxidative damage. To address this, we developed a novel multifunctional hydrogel (SPA) by crosslinking sericin (SS), protocatechualdehyde (PA), and silver sulfadiazine (AgSD). The SPA hydrogel integrates high transparency, excellent breathability, superior moisturizing capacity, tunable gelation kinetics, good elasticity, suitable adhesive strength and pH-responsive swelling/degradation/release. It exhibits potent free radical scavenging activity, achieving over 80% clearance of both DPPH and ABTS radicals, alongside broad-spectrum and powerful antibacterial efficacy against Staphylococcus aureus ( S. aureus ) , Pseudomonas aeruginosa ( P. aeruginosa ), and Escherichia coli ( E. coli ). Moreover, the hydrogel promotes excellent cell adhesion, cytocompatibility, and rapid hemostasis. In the S.aureus -infected chronic wound model, SPA significantly accelerated wound closure and enhanced tissue regeneration. This work presents an integrated therapeutic strategy that combines real-time visual observation, on-demand antibacterial action, and proactive repair facilitation, thereby underscoring the potential of natural biomaterials in advanced wound management.

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Acta Biomaterialia · 2024 · IF 9.4

Adhesive hydrogel releases protocatechualdehyde-Fe3+ complex to promote three healing stages for accelerated therapy of oral ulcers

Yue Wang,Ziyi Pan,Jing Cui,Xu Zhang,Daowei Li,Hongchen Sun,Bai Yang,Yunfeng Li

ABSTRACT Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe 3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. Statement of significance By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe 3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.

研究领域: 生物医学工程 · 药学 · 组织工程 · 伤口愈合
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RSC Advances · 2019 ·Vol. 9 ·期 53 ·30815-30822 · IF 3.049

A biobased Schiff base from protocatechualdehyde and its application in flame-retardant, low-smoke epoxy resin systems

Weiqi Xie,Shiwen Huang,Shumei Liu,Jianqing Zhao

Herein, a new renewable Schiff base flame retardant 4,4′-((1E,1′E)-((oxybis(4,1-phenylene))bis(azanylylidene))bis(methanylylidene))bis(benzene-1,2-diol) (PH-ODA) was prepared by the reaction of protocatechualdehyde with 4,4′-diaminodiphenyl ether (ODA). PH-ODA (acting as a carbonization agent) combined with ammonium polyphosphate (APP) were used as intumescent flame retardants for commercial bisphenol A epoxy resin (DGEBA). For the cured epoxy resin containing 7.5% APP and 2.5% PH-ODA, the limiting oxygen index (LOI) reached 29.9% (with the V-0 rating in UL-94 test), and the peak heat release rate and total smoke production were respectively decreased by 88.1% and 68.3%, compared with pure epoxy resin. The enhancement of fire-safety performance was due to PH-ODA/APP promoting the formation of a compact intumescent char structure. It was also found that the synergism between PH-ODA and APP was helpful to enhance the fire resistance of the epoxy matrix. This work provides a facile and sustainable route for synthesizing Schiff base compounds from biomass-derived resources, possessing great potential for application in highly-effective intumescent flame retardants.

研究领域: 高分子科学 · 材料化学 · 火灾安全工程 · 可持续化学 · 阻燃材料
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Enzyme-crosslinked protocatechualdehyde acetal-modified polyvinyl alcohol hydrogel with acid-responsive and emerging photothermal properties for infected skin wound management

Hua Zhao,Yachao Yu,Jingmei Liu,Wenzhi Yang,Zhijie Zhao,Yongli Liu,Fangxia Guan,Minghao Yao

External pathogens and underlying diseases often complicate the wound microenvironment and hinder healing. The combination of plant polyphenols and photothermal therapy offers multiple advantages for skin wound repair and represents a promising alternative to conventional antibiotics. However, most plant polyphenols are susceptible to chemical degradation and inherently lack photothermal responsiveness. In this study, protocatechualdehyde (PA), a plant polyphenol with diverse bioactivities, was selected. Polyvinyl alcohol (PVA) was modified through acetalization with PA to obtain polyvinyl protocatechualdehyde acetal (PPA). Subsequently, the catechol groups of PA were enzymatically cross-linked using HRP/H₂O₂ to form a hydrogel. This acetal-grafting strategy not only shielded the functional groups of PA from excessive degradation, but also conferred acid-responsive properties to the hydrogel, thereby facilitating the sustained release of bioactive PA and its oligomers at the acidic microenvironment of the wound. Although native PA lacks photothermal activity, the HRP/H₂O₂-induced formation of dimeric and oligomeric PA structures endowed the hydrogel with intrinsic photothermal responsiveness, eliminating the need for additional photothermal agents. The PPA hydrogel exhibited excellent adhesion, hemostatic performance, photothermal conversion efficiency, antioxidant, antibacterial properties, and biocompatibility. When combined with photothermal therapy in a mouse infected wound model, the PPA hydrogel significantly accelerated wound closure, reduced local inflammation, promoted tissue regeneration and collagen deposition, highlighting its potential in skin wound repair.

CAS / MDL: 9003-99-0
研究领域: 生物材料 · 高分子科学 · 组织工程 · 伤口修复 · 光热治疗 · 生物医学工程 · 药剂学 · 纳米医学
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Frontiers in Pharmacology · 2022 · IF 5.988

Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

Shidong Cao,Senmiao Chen,Xilin Qiao,Yan Guo,Fang Liu,Zhishan Ding,Bo Jin

Background: Oxidative stress-induced endothelial cell death, such as apoptosis and autophagy, plays a critical role in ischemia-reperfusion injury. Protocatechualdehyde (PCA) is a major bioactive component of the traditional Chinese medicine Salvia miltiorrhiza Bunge (Lamiaceae), and it has been proved to be effective in the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases. However, its role in oxidative stress-induced endothelial cell death and its underlying mechanisms remains unclear. This study aims to investigate the effects and mechanisms of PCA on endothelial cell apoptosis and autophagy induced by oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Methods: After OGD/R induction, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of PCA. Cell viability, apoptosis, and autophagy were detected by Cell Counting Kit-8 assay, flow cytometry, and monodansylcadaverine assay, respectively. Western blot was applied to explore the effects of PCA on the expression levels of relevant protein factors. Results: The results show that PCA significantly promoted cell survival rate and cell proliferation and enhanced the antioxidant activity in OGD/R-induced HUVECs. PCA inhibited HUVECs apoptosis, as evidenced by decreased expression of cleaved-caspase-3, Bcl2-associated X (BAX), and increased expression of Bcl-2. PCA induced autophagy by reducing the expression of P62 while increasing the expression of Beclin-1 and LC3 II/I. Meanwhile, PCA enhanced the expression of Sirtuin 1 (SIRT1) and suppressed the expression of P53. When SIRT1 was inhibited by selisistat or SIRT1 small-interfering RNA, the anti-apoptotic and pro-autophagy abilities of PCA were attenuated. Conclusion: These results demonstrated that PCA rescued HUVECs from OGD/R-induced injury by promoting autophagy and inhibiting apoptosis through SIRT1 and could be developed as a potential therapeutic agent against ischemic diseases.

CAS / MDL: 7601-90-3
研究领域: 药理学 · 细胞生物学 · 神经科学 · 心血管疾病
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