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Chemical Biology and Drug Design
APRIL 28, 2024
Cover Image © molekuul_be/Shutterstock.
Chemical Biology and Drug Design
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Chemical Biology and Drug Design
APRIL 2, 2024
Cover Image © molekuul_be/Shutterstock.
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Role of autophagy and proteostasis in neurodegenerative diseases: Exploring the therapeutic interventions
Chemical Biology and Drug Design
APRIL 3, 2024
The present review explores the intricate relationship between autophagy and proteostasis in the pathogenesis of neurodegenerative diseases along with the therapeutic interventions to mitigate the same. Abstract Neurodegenerative disorders are devastating disorders characterized by gradual loss of neurons and cognition or mobility impairment. The common pathological features of these diseases are associated with the accumulation of misfolded or aggregation of proteins.
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Diosgenin inhibits proliferation and migration of ovarian cancer cells and induce apoptosis via upregulation of PTEN
Chemical Biology and Drug Design
MARCH 27, 2024
Diosgenin through downregulation of PI3K, Akt, mTOR and upregulation of PTEN inhibits migration and proliferation of OVCAR-3 cancer cells. Abstract Diosgenin, a natural steroidal sapogenin, has recently attracted a high amount of attention, as an effective anticancer agent in ovarian cancer. However, diosgenin mediated anticancer impacts are still not completely understood.
Melatonin and its bioisosteres as potential therapeutic agents for the treatment of retinopathy of prematurity
Chemical Biology and Drug Design
MARCH 13, 2024
Administration of melatonin and 3 its bioisosters efficiently normalize VEGF-A and total protein levels and antioxidant activity in vitreous body of newborn rat pups (in oxygen-induced retinopathy model). Novel melatonin analogues could be used as new metabolically stable therapeutic agents for the treatment of retinopathy of prematurity. Abstract We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1 – 3 ) on the development of oxyg
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Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC?MS/MS cancer cell entrapment assays
Chemical Biology and Drug Design
MARCH 11, 2024
Polymerase inhibitor (daclatasvir; DLT) does not induce cell proliferation in variable cell lines. DLT exhibited a superior antiproliferative and anti-CDK1 potential over the nucleoside analogues, especially in the HepG2. This supports the claim that a reduction in HCC development in patients treated with a DAA. Abstract Directly acting antivirals (DAAs) are a breakthrough in the treatment of HCV.
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Brucine alleviates fibroblast?like synoviocytes dysfunction and inflammation by regulating YY1 during rheumatoid arthritis
Chemical Biology and Drug Design
MARCH 8, 2024
Brucine suppressed the proliferation, migration, invasion, inflammation, and macrophage M1 polarization, as well as induced apoptosis in RA-FLSs by decreasing YY1 via circ_0139658/miR-653-5p axis. Abstract Brucine is a weak alkaline indole alkaloid with wide pharmacological activities and has been identified to protect against rheumatoid arthritis (RA) process.
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Saikosaponin D mitigate pilocarpine?induced astrocyte injury by regulating the NLRP3/caspase?1 signaling pathway
Chemical Biology and Drug Design
MARCH 8, 2024
Saikosaponin D (SSD) was used to treat pilocarpine (PP)-induced primary astrocyte injury model in rats. SSD was proved to enhance cell viability, inhibit inflammatory and oxidative stress responses, and improve mitochondrial dysfunction, thus playing a neuroprotective role in the PP-induced primary astrocyte injury model. Abstract Studies have shown that saikosaponin D (SSD) has favorable neurotherapeutic effects.
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Synthesis, in silico screening, and biological evaluation of novel pyridine congeners as anti?epileptic agents targeting AMPA (??amino?3?hydroxy?5?methylisoxazole) receptors
Chemical Biology and Drug Design
MARCH 7, 2024
Synthesis, in silico screening, and anti-epileptic activity of novel pyridine analogs. Abstract The research involves the synthesis of a series of new pyridine analogs 5(i-x) and their evaluation for anti-epileptic potential using in silico and in vivo models. Synthesis of the compounds was accomplished by using the Vilsmeier-Haack reaction principle.
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Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents
Chemical Biology and Drug Design
MARCH 7, 2024
A new class of quinoxaline aryl ether compounds was designed and synthesized. These compounds were tested on HCT-116, MDA-MB-231, and DU-145 cancer lines. The three cancer cell lines responded best to FQ and MQ, which were investigated for apoptosis. Molecular docking/dynamic studies of FQ and MQ at c-Met kinase (PDB: 3F66) were also done. Abstract We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with vari
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Ag2O?TiO2?NTs enhance osteogenic activity in vitro by modulating TNF??/??catenin signaling in bone marrow?derived mesenchymal stem cells
Chemical Biology and Drug Design
MARCH 7, 2024
BMSCs were isolated from the femurs of SD rats aged 7–8 weeks and identified by flow cytometry. BMSCs were inoculated into Ag2O-TiO2-NTs and added into stem cell osteogenic induction differentiation culture medium. Extracellular LDH enzyme activity was detected at 7 and 14 days of induction, respectively, and osteogenic genes in BMSCs were detected by qRT-PCR.
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Computational analysis followed by in vitro studies to explore cytokines (TNF??, IL?6 and IL?1?) inhibition potential of the new natural molecule polonilignan
Chemical Biology and Drug Design
MARCH 6, 2024
Computational analysis and in vitro studies corroborated the cytokines (TNF-α, IL-6 and IL-1β) inhibition potential of the new natural molecule polonilignan. Abstract Targeting pro-inflammatory cytokines and their production is found to be of therapeutic benefit for the regulation of inflammation in various chronic autoimmune diseases. Our continued efforts to discover small molecular-weight pro-inflammatory cytokine inhibitors resulted in identifying a novel natural lignan molecule named poloni
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??Sitosterol attenuates anlotinib resistance in non?small cell lung cancer cells by inhibiting miR?181a?3p/SHQ1 signaling
Chemical Biology and Drug Design
MARCH 4, 2024
A549 cells were treated with different concentrations of anlotinib to create anlotinib-resistant A549 cells (A549/anlotinib cells). miR-181a-3p mimics were transfected into A549/anlotinib cells. Meanwhile, A549 and A549/anlotinib cells were treated with β-sitosterol at different concentrations. Cell Counting Kit-8 (CCK-8) was used to measure cell proliferation.
Role of Qufeng Tongqiao Prescription in the protection of cerebral ischemia and associated molecular network mechanism
Chemical Biology and Drug Design
MARCH 3, 2024
Study on the mechanism of graph Qufeng Tongqiao Prescription in the treatment of cerebral ischemia through network pharmacology combined with animal experiments. Abstract To explore the of Qufeng Tongqiao Prescription in the treatment of cerebral ischemia–reperfusion (CIR) and associated molecular network mechanism. Venny diagram, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis, protein–protein interaction (PPI), hub genes mining, molecular docking, combined with a
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Methyltransferase METTL3?mediated maturation of miR?4654 facilitates high glucose?induced apoptosis and oxidative stress in lens epithelial cells via decreasing SOD2
Chemical Biology and Drug Design
FEBRUARY 26, 2024
Methyltransferase METTL3-mediated maturation of miR-4654 promotes high glucose-induced apoptosis, oxidative stress, and viability inhibition in lens epithelial cells via decreasing SOD2. Abstract N6-methyladenosine (m 6 A) modification has been reported to have roles in modulating the development of diabetic cataract (DC). Methyltransferase-like 3 (METTL3) is a critical m 6 A methyltransferase involving in m 6 A modification activation.
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Cinnamaldehyde protects cardiomyocytes from oxygen?glucose deprivation/reoxygenation?induced lipid peroxidation and DNA damage via activating the Nrf2 pathway
Chemical Biology and Drug Design
FEBRUARY 26, 2024
Cinnamaldehyde can enhance cell viability and inhibit cell apoptosis of H9C2 cardiomyocytes induced by oxygen-glucose deprivation/reoxygenation. The mechanism research revealed that cinnamaldehyde activated the Nrf2 pathway to attenuate lipid peroxidation and repair DNA damage to protect cardiomyocytes from ischemia/reperfusion injury in the OGD/R-induced H9C2 cardiomyocyte model.
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100 Isoliquiritigenin attenuates neuroinflammation after subarachnoid hemorrhage through inhibition of NF??B?mediated NLRP3 inflammasome activation
Chemical Biology and Drug Design
FEBRUARY 23, 2024
In the present work, we report that isoliquiritigenin, a bioactive component of licorice roots, attenuates neuroinflammation of a mice model with subarachnoid hemorrhage through inhibition of NF-κB-mediated NLRP3 inflammasome activation. This work suggests that isoliquiritigenin may ameliorate neurological injury of the patients with subarachnoid hemorrhage, as a kind of adjuvant therapy.
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100 TMEM97 knockdown inhibits 5?fluorouracil resistance by regulating epithelial?mesenchymal transition and ABC transporter expression via inactivating the Akt/mTOR pathway in 5?fluorouracil?resistant colorectal cancer cells
Chemical Biology and Drug Design
FEBRUARY 22, 2024
TMEM97 knockdown re-sensitized HCT116/R and SW480/R cells to 5-FU by inhibiting EMT and ABC transporter expression through inactivation of Akt/mTOR pathway. These results indicate that TMEM97 may be a promising therapeutic target to combat 5-FU resistance in CRC. Abstract Resistance to 5-fluorouracil (5-FU) is still a primary setback to the success of colorectal cancer (CRC) chemotherapy.
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Piceatannol selectively inhibited the JNK3 enzyme and augmented apoptosis through inhibition of Bcl?2/Cyt?c/caspase?dependent pathways in the oxygen–glucose deprived SHSY?5Y cell lines: In silico and in vitro study
Chemical Biology and Drug Design
FEBRUARY 21, 2024
JNK3 serves as a neuronal kinase with the capacity for activation upon exposure to stress response like oxygen–glucose deprivation. Upon phosphorylation and activation, JNK3 relocates to the mitochondria, where it is thought to enhance the permeability of the mitochondrial outer membrane (MOMP). This heightened MOMP leads to the release of Cyt-c into the cytoplasm, forming a complex with apaf-1 that triggers enzyme activation.
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Design, synthesis, and evaluation of novel bistrifluoromethyl?based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease
Chemical Biology and Drug Design
FEBRUARY 20, 2024
Synthesis of 22 novel bistrufluoromethyl-derived hydrazide hydrazones. AChE, hCA I, and hCA II activity evaluation. Compound displayed potent activities against AChE, hCAI, and hCAII. Abstract In this project, non-sulfonamide bistrifluoromethyl-derived hydrazide-hydrazones were synthesized as multi-target-directed ligands to treat Alzheimer's disease and then, the novel derivatives were characterized by diverse spectral methods.
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IGF2BP3 loss inhibits cell progression by upregulating has_circRNA_103820, and hsa_circRNA_103820?encoded peptide inhibits cell progression by inactivating the AKT pathway in lung cancer
Chemical Biology and Drug Design
FEBRUARY 20, 2024
Hsa_circRNA_103820, downregulated by IGF2BP3, could encode a 188-aa peptide and inhibited lung cancer cell malignant progression by inhibiting the AKT pathway. Abstract N6-methyladenosine (m6A) modification and m6A-related RNA-binding proteins (RBPs) play vital roles in various aspects of circRNA metabolism. Hsa_circRNA_103820 is implicated in the pathogenesis of multiple cancers, including lung cancer (LC).
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Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/??catenin
Chemical Biology and Drug Design
FEBRUARY 19, 2024
Icariin promoted BMSC osteogenic differentiation via enhancing cell viability, ALP activity, mineralization levels, OCN, and OPN levels by mediating the USP47/SIRT1/Wnt/β-catenin pathway. Abstract Icariin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying molecular mechanism by which Icariin regulates osteogenic differentiation needs to be further revealed.
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Sinigrin improves cerebral ischaemia?reperfusion injury by inhibiting the TLR4 pathway?mediated oxidative stress
Chemical Biology and Drug Design
FEBRUARY 18, 2024
Sinigrin Protects the Brain from CIR Injury by Reducing Oxidative Stress and Inhibiting the TLR4 Signaling Pathway. Abstract Cerebral ischaemia-reperfusion (CIR) injury occurs in stroke patients after the restoration of cerebral perfusion. Sinigrin, a phytochemical found in cruciferous vegetables, exhibits strong antioxidant activity. This study investigated the role of sinigrin in oxidative stress using a CIR injury model.
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100 Prostaglandin E2 may clinically alleviate dry eye disease by inducing Th17 cell differentiation
Chemical Biology and Drug Design
FEBRUARY 15, 2024
Prostaglandin E2 (PGE) promotes inflammation in the dry eye (DE) by promoting Th17 cell differentiation through its receptor EPs. Abstract Dry eye (DE) is a multifactorial ocular surface disease characterised by an imbalance in tear homeostasis. The pathogenesis of DE is complex and related to environmental, immunological (e.g., T helper 17 cells) and other factors.
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Nitrogen?containing heterocyclic compounds: A ray of hope in depression?
Chemical Biology and Drug Design
FEBRUARY 15, 2024
Role of serotonin, dopamine, and norepinephrine in neural functions and symptoms involved during their altered levels. Abstract Depression is not similar to daily mood fluctuations and temporary emotional responses to day-to-day activities. Depression is not a passing problem; it is an ongoing problem. It deals with different episodes consisting of several symptoms that last for at least 2 weeks.
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Synthesis and in vitro evaluation of antibacterial and antibiofilm activities of novel triphenylphosphonium?functionalized substituted pyrimidines
Chemical Biology and Drug Design
FEBRUARY 14, 2024
In this study, triphenylphosphonium-containing substituted pyrimidines were synthesized and evaluated for their antibacterial and antibiofilm activities against S. aureus 222 , E. coli 311 , and P. aeruginosa 449. Compounds 2a and 11 showed a significant reduction in biofilm formation of S. aureus 222 and E. coli 311 by 76.5%–99.1%. Abstract The increase in the prevalence of antibiotic-resistant pathogens leads to a decrease in the number of antimicrobial agents for the treatment of infections a
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Design, synthesis, and anticancer evaluation of alkynylated pyrrole derivatives
Chemical Biology and Drug Design
FEBRUARY 14, 2024
The discovery of alkynylated pyrrole derivatives as anticancer agents. Abstract A series of alkynylated pyrrole derivatives were meticulously designed, drawing inspiration from the structure of 3-alkynylpyrrole-2,4-dicarboxylates, which were synthesized via a cyclization process involving methylene isocyanides and propiolaldehydes under mild conditions.
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A recent update on huprine and its hybrids as a potential multifunctional agent for the treatment of Alzheimer's disease
Chemical Biology and Drug Design
FEBRUARY 13, 2024
Alzheimer's disease (AD) is a common age-related neurodegenerative brain disorder characterized by the impairment in memory and other cognitive functions. Although there is currently no successful pharmacotherapy for AD, and researchers are continuously exploring the various pathogenesis of AD to develop potential therapeutic drugs. Abstract Alzheimer's disease (AD) is a common age-related neurodegenerative brain disorder characterized by the impairment in memory and other cognitive functions.
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100 Network pharmacology and in vitro experiments reveal sophoridine?induced apoptosis and G1 phase arrest via ROS?dependent PI3K/Akt/FoxO3a pathway activation in human bladder cancer cells
Chemical Biology and Drug Design
FEBRUARY 12, 2024
Schematic diagram of the mechanism of sophoridine-induced apoptosis and cycle arrest in BLCA. Abstract Bladder cancer (BLCA), a common primary malignancy, exhibits resistance to conventional chemotherapeutic agents. Sophoridine (SR) is a quinoline alkaloid derived from the traditional Chinese herb Sophora alopecuroides L., which belongs to the legume family Sophoraceae.
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100 Hydromorphone hydrochloride preconditioning combined with postconditioning attenuates myocardial ischemia/reperfusion injury in rats by improving mitochondrial function and activating the PI3K/Akt signaling pathway
Chemical Biology and Drug Design
FEBRUARY 11, 2024
Hydromorphone hydrochloride (HH) attenuates myocardial ischemia/reperfusion injury in rats by by promoting mitochondrial biogenesis to improve mitochondrial function and reduce oxidative stress, and activating the PI3K/Akt signaling pathway. HH preconditioning combined with postconditioning showed optimal efficacy. Abstract Thrombolytic therapy or percutaneous coronary intervention for myocardial infarction often cause myocardial ischemia/reperfusion injury (MIRI) and poor prognosis of patients.
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Synthesis of peiminine derivatives and its effect on A549 lung cancer?bearing mice
Chemical Biology and Drug Design
FEBRUARY 7, 2024
We obtained a total of 14 new compounds from peiminine and found that compound 1c has strong cytotoxicity and can inhibit cell proliferation. qRT-PCR and western blot showed that compound 1c exhibits an inhibitory effect on lung cancer, which was found to occur via inhibition of the PI3K/AKT/mTOR/NF-κB signaling pathway. Abstract To seek an effective anti-lung cancer drug, a total of 14 derivatives were synthesized and characterized.
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100 HSYA prevents IL?1??induced human chondrocyte damage in osteoarthritis by inhibiting NF??B activation
Chemical Biology and Drug Design
FEBRUARY 7, 2024
HSYA has been found to inhibit the expression of MMP13, COL2A1, SOX9, IL-6, and TNF-α in IL-1β-induced osteoarthritis. Additionally, HSYA exhibits anti-inflammatory effects, potentially by inhibiting the activation of the NF-κB signaling pathway induced by IL-1β. Abstract The progression of osteoarthritis (OA) requires the involvement of inflammation, in which chondrocyte damage plays a significant role.
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Miltirone suppresses ESCC cell viability and invasion by promoting E3 ligase mediated?FZD2 ubiquitination and degradation
Chemical Biology and Drug Design
FEBRUARY 7, 2024
Schematic diagram of mitirone-inhibited ESCC. Mitirone inhibits the RSPO-mediated ZNRF3/RNF43 degradation mechanism by reducing the expression of RSPO1 and RSPO2 in ESCC cell lines K30 and K150. The red box indicates the ubiquitination and degradation mechanism of FZD2 under the action of mitirone. Abstract Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer and lacks effective treatment.
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100 Glycyrrhetinic acid alleviates atrial fibrillation by inhibiting the expression of PIM1
Chemical Biology and Drug Design
FEBRUARY 6, 2024
By dint of a relatively high content of glycyrrhetinic acid (GA), radix glycyrrhizae preparata is often adopted to treat atrial fibrillation (AF). Thus, the mechanism of GA was expounded in our study. Our research concludes that GA alleviates AF through suppressing the expression of PIM1. Abstract Glycyrrhetinic acid (GA) is known to exert a cardioprotective effect, while its mechanism in atrial fibrillation (AF) remains poorly defined.
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Capsaicin derivatives: Synthesis and biological activity
Chemical Biology and Drug Design
FEBRUARY 5, 2024
The synthesis, biological activity, and the structure–activity relationship of capsaicin and its derivatives are reviewed. Furthermore, we detailly describe the combination mechanism between capsaicin and TRPV1, TRPV1 related capsaicin derivatives as well. Abstract Capsaicin is the main active ingredient of chili peppers and the most pungent alkaloid.
100 Could natural terpenes be an alternative for the treatment of neglected tropical diseases?
Chemical Biology and Drug Design
FEBRUARY 2, 2024
Terpenes are compounds that inhibit the growth of Leishmania spp, Schistosoma spp, and Echinococcus spp, cause changes in parasite ultrastructure, inhibit enzyme activity, and modulate the immune response. Their use in combination therapy decreases the concentration of the reference drug used. Abstract Existing chemotherapy for neglected tropical diseases (NTDs) can often be toxic and ineffective, highlighting the necessity for new treatments.
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100 Synthesis, molecular docking, QSTR and in?silico ADME studies of novel 1,3?thiazolidine?amide derivatives as hybrid bioactive heterocycles
Chemical Biology and Drug Design
JANUARY 29, 2024
A series of 1,3-thiazolidine- amide derivatives were synthesized via two different methods (microwave irradiation and conventional). These derivatives exhibited in vitro good to excellent antimicrobial activity. Molecular docking study performed on the crucial antifungal target 4WMZ. Quantitative structure toxicity relationship (QSTR) study pointed out the slight toxic nature of compounds.
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100 Inhibition of O6?methylguanine?DNA?methyltransferase (MGMT) by lomeguatrib reduces multiple myeloma cell viability and impairs DNA repair in MGMT?proficient cells
Chemical Biology and Drug Design
JANUARY 29, 2024
MGMT mRNA expression was significantly increased in CD138+ myeloma cells compared with their matched CD138-nontumorigenic cells and inhibition of MGMT by its specific inhibitor lomeguatrib in MM cells reduced DNA repair, cell viability, and S phase entry and increased DNA damage and apoptosis. Apoptosis and DNA damage were further elevated in melphalan-treated RPMI 8226 cells, where MGMT expression is absent.
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100 Crocin enhances the sensitivity to paclitaxel in human breast cancer cells by reducing BIRC5 expression
Chemical Biology and Drug Design
JANUARY 29, 2024
Crocin enhances the sensitivity of breast cancer cells to PTX by suppressing BIRC5 expression. Our data identified crocin as a novel promising therapeutic agent in sensitizing breast cancer cells to PTX, and highlighted the potential role of BIRC5 in the development of PTX resistance in breast cancer. Abstract Paclitaxel (PTX) is one of the first-line chemotherapeutic agents for treating breast cancer.
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100 Interactions of small molecule inhibitors with secreted phospholipase A2: A review of the structural data
Chemical Biology and Drug Design
JANUARY 29, 2024
Due to their roles in inflammation, the sPLA 2 enzymes are of much medicinal interest. sPLA 2 inhibitors have been developed for the treatment of inflammatory and other conditions such as cardiovascular disease, arteriosclerosis and rheumatoid arthritis. To aid the medicinal chemist in the design of sPLA 2 inhibitors, this review selected four human sPLA 2 s and presented the characteristics of the bound inhibitors that are considered key for high-affinity interaction.
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The (patho)physiological roles of the individual deacylase activities of a sirtuin
Chemical Biology and Drug Design
JANUARY 29, 2024
An account on the currently limited knowledge generated with a still thin repertoire of genetic/chemical tools on the (patho)physiological roles of the individual deacylase activities of sirtuins is presented, calling for an expanded research to ultimately sort out the (patho)physiological roles of all the deacylase activities indicated in this figure.
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100 Design, antitumor, and anti?Ras activity of propynyl?substituted harmine bases
Chemical Biology and Drug Design
JANUARY 24, 2024
Compound 9i, a derivative of harmine with anticancer activity, was synthesized and characterized. The results of molecular docking and molecular dynamics simulations the complex (9i and DYRK1A kinase) was compact and stable. In addition, Compound 9i may be useful as a pro-oxidant for cancers caused by Ras over-activation. Abstract Modifications at the harmine (HAM) 9-N position demonstrated effective antitumor activity in previous studies.
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Network pharmacology analysis and experimental evaluations of YH complex on androgenetic alopecia by regulating the androgenic?apoptotic axis
Chemical Biology and Drug Design
JANUARY 24, 2024
YH complex, consisting C. cassia and A. membranaceus , effectively promoted hair regeneration through the network pharmacology-derived prediction and experimental confirmation in testosterone-induced AGA mice. A new herbal formula, YH complex, might be an effective treatment for androgenetic alopecia. Abstract Cinnamomum cassia and Astragalus membranaceus have been used as traditional medicines as well as functional foods worldwide, but its hair growth properties have been verified yet.
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100 Baicalin alleviates oxygen–glucose deprivation/reoxygenation?induced SK?N?SH cell injury via the regulation of miR?556?3p/ACSL4 pathway
Chemical Biology and Drug Design
JANUARY 24, 2024
Baicalin alleviates OGD/R-induced SK-N-SH cell apoptosis, inflammation, and ferroptosis in vitro, and brain injury in MCAO mice in vivo, via the regulation of miR-556-3p/ACSL4 pathway. Abstract Baicalin (BCL) has been found to have neuroprotective effects in ischemic stroke (IS), but its underlying molecular mechanisms are unknown. SK-N-SH cells were treated with BCL and then induced by oxygen–glucose deprivation/reoxygenation (OGD/R).
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