Chinese herbal medicine compound of flavonoids adjunctive treatment for oral cancer.

Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and chemotherapy are available but may have adverse effects. Molecular gene therapy, focusing on genetic mutations linked to oral cancer, presents a promising alternative.In this study, we evaluated 27 chemotherapeutic drugs and 63 Chinese herbal medicines for their effectiveness, categorized them by their cellular mechanisms, and identified potential adjuvant therapy candidates for oral cancer. Our findings highlight the impact of natural flavonoids on oral cancer cells, inducing apoptosis, and confirming their potential in molecular genetic analysis. In conclusion, the natural compounds present in Chinese herbal medicine, particularly flavonoids, offer a promising avenue to target specific genetic mutations in oral cancer cells. This approach may reduce the risks associated with oral cancer treatment and pave the way for innovative adjuvant therapies.

Combinations of scalp acupuncture location for the treatment of post-stroke hemiparesis: A systematic review and Apriori algorithm-based association rule analysis.

Background: Post-stroke hemiparesis strongly affects stroke patients' activities of daily living and health-related quality of life. Scalp acupuncture (SA) is reportedly beneficial for post-stroke hemiparesis. However, there is still no standard of SA for the treatment of post-stroke hemiparesis. Apriori algorithm-based association rule analysis is a kind of "if-then" rule-based machine learning method suitable for investigating the underlying rules of acupuncture point/location selections. This study aimed to investigate the core SA combinations for the treatment of post-stroke hemiparesis by using a systematic review and Apriori algorithm-based association rule analysis. Methods: We conducted a systematic review to include relevant randomized controlled trial (RCT) studies investigating the effects of SA treatment in treating patients with post-stroke hemiparesis, assessed by the Fugl-Meyer Assessment (FMA) score. We excluded studies using herbal medicine or manual acupuncture. Results: We extracted 33 SA locations from the 35 included RCT studies. The following SA styles were noted: International Standard Scalp Acupuncture (ISSA), WHO Standard Acupuncture Point Locations (SAPL), Zhu's style SA, Jiao's style SA, and Lin's style SA. Sixty-one association rules were investigated based on the integrated SA location data. Conclusions: SAPL_GV20 (Baihui), SAPL_GV24 (Shenting), ISSA_MS6_i (ISSA Anterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_MS7_i (ISSA Posterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_PR (ISSA Parietal region, comprised of ISSA_MS5, ISSA_MS6, ISSA_MS7, ISSA_MS8, and ISSA_MS9), and SAPL_Ex.HN3 (Yintang) can be considered the core SA location combination for the treatment of post-stroke hemiparesis. We recommend a core SA combination for further animal studies, clinical trials, and treatment strategies.

Wild Bitter Melon Extract Abrogates Hypoxia-Induced Cell Death via the Regulation of Ferroptosis, ER Stress, and Apoptosis in Microglial BV2 Cells.

Microglial cells are well-known phagocytic cells that are resistant to the central nervous system (CNS) and play an important role in the maintenance of CNS homeostasis. Activated microglial cells induce neuroinflammation under hypoxia and typically cause neuronal damage in CNS diseases. In this study, we propose that wild bitter melon extract (WBM) has a protective effect on hypoxia-induced cell death via regulation of ferroptosis, ER stress, and apoptosis. The results demonstrated that hypoxia caused microglial BV-2 the accumulation of lipid ROS, ferroptosis, ER stress, and apoptosis. In this study, we investigated the pharmacological effects of WBM on BV-2 cells following hypoxia-induced cell death. The results indicated that WBM reversed hypoxia-downregulated antiferroptotic molecules Gpx4 and SLC7A11, as well as upregulated the ER stress markers CHOP and Bip. Moreover, WBM alleviated hypoxia-induced apoptosis via the regulation of cleaved-caspase 3, Bax, and Bcl-2. Our results suggest that WBM may be a good candidate for preventing CNS disorders in the future.

Acupuncture and Traditional Chinese Herbal Medicine Integrated With Conventional Rehabilitation for Post-stroke Functional Recovery: A Retrospective Cohort Study.

Background: Stroke leads to tremendous impacts on patients and the healthcare system. It is crucial to explore the potential management of rehabilitation. Acupuncture and traditional Chinese herbal medicine (TCHM) integrated with conventional rehabilitation benefit post-stroke functional recovery. Methods: We retrospectively reviewed the medical records of all patients included in the Integrated Traditional Chinese-Western Medicine care program for stroke (ITCWM-stroke care program) in 2019 in Taipei Tzu Chi Hospital to investigate the effects of acupuncture and TCHM integrated with conventional rehabilitation on National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores before and after the program. Results: A total of 255 stroke inpatients were retrieved and divided into acupuncture and acupuncture + TCHM group by hemorrhagic and ischemic stroke types, respectively. All the patients were recruited in the program at the early subacute phase after stroke onset. Of the hemorrhagic and ischemic stroke subjects, the NIHSS and BI total scores were significantly improved in the acupuncture and acupuncture + TCHM groups. The subgroup analysis results showed that in subjects with a baseline BI score ≤ 40, the acupuncture + TCHM group significantly improved BI total score better than the acupuncture group in both hemorrhagic (p < 0.05) and ischemic (p < 0.05) stroke subjects. Conclusion: Acupuncture and TCHM integrated with conventional rehabilitation significantly improve stroke patients' functional recovery at the early subacute phase. Acupuncture + TCHM contributes to better activities of daily living (ADL) improvements in stroke patients with a baseline BI score ≤ 40. We suggest integrating acupuncture and TCHM into the post-stroke rehabilitation strategy, especially for stroke patients with poor ADL function.

Combined Acupoints for the Treatment of Patients with Obesity: An Association Rule Analysis.

Obesity is a prevalent metabolic disease that increases the risk of other diseases, such as hypertension, diabetes, hyperlipidemia, cardiovascular disease, and certain cancers. A meta-analysis of 11 randomized sham-controlled trials indicates that acupuncture had adjuvant benefits in improving simple obesity, and previous studies have reported that acupoint combinations were more useful than single-acupoint therapy. The Apriori algorithm, a data mining-based analysis that finds potential correlations in datasets, is broadly applied in medicine and business. This study, based on the Apriori algorithm-based association rule analysis, found the association rules of acupoints among 11 randomized controlled trials (RCTs). There were 23 acupoints extracted from 11 RCTs. We used Python to calculate the association between acupoints and disease. We found the top 10 frequency acupoints were Extra12, TF4, LI4, LI11, ST25, ST36, ST44, CO4, CO18, and CO1. We investigated the 1118 association rule and found that {LI4, ST36} ≥ {ST44}, {LI4, ST44} ≥ {ST36}, and {ST36, ST44} ≥ {LI4} were the most associated rules in the data. Acupoints, including LI4, ST36, and ST44, are the core acupoint combinations in the treatment of simple obesity.

An Association Rule Analysis of the Acupressure Effect on Sleep Quality.

BACKGROUND: Sleep is recognized as an all-important physiological process, which also contributes to maintaining several bodily functions and systems. According to the Pittsburgh Sleep Quality Index (PSQI), also known as the most widely used tool in the field of subjective assessment of self-perceived sleep quality, a combination of acupoints could be more effective than single acupoint treatment in improving sleep quality. METHODS: The present study was based on the extracted eligible studies rooted in a previous meta-analysis that worked on the basis of association rule mining and examined the potential kernel acupoint combinations for improving sleep quality. RESULTS: Depending on the Apriori algorithm, we summarized 26 acupoints as binary data from the 32 eligible studies based on a previous meta-analysis and analyzed them. The top 10 most frequently selected acupoints were HT7, SP6, PC6, KI1, GV20, EM5, EX-HN3, EX-HN16, KI3, and MA-TF1. Furthermore, as deduced from 21 association rules, the primary relevant rules in the combination of acupoints are (EX-HN3, EX-HN16)=>(GV20) and (HT7, KI1)=>(PC6). CONCLUSIONS: In order to use acupuncture to improve sleep quality, integrating (EX-HN3, EX-HN16, GV20) with (HT7, KI1, PC6) acupoints could be deemed as the kernel acupoint combination.

Nephroprotective Role of Chrysophanol in Hypoxia/Reoxygenation-Induced Renal Cell Damage via Apoptosis, ER Stress, and Ferroptosis.

Acute kidney injury (AKI) is caused by hypoxia-reoxygenation (H/R), which is a kidney injury produced by a variety of causes, resulting in the remaining portion of the kidney function being unable to maintain the balance for performing the tasks of waste excretion metabolism, and electrolyte and acid-base balance. Many studies have reported the use of Chinese medicine to slow down the progression and alleviate the complications of chronic renal failure. Chrysophanol is a component of Rheum officinale Baill, a traditional Chinese medicine that has been clinically used to treat renal disease. We aimed to study the nephroprotective effect of chrysophanol on hypoxia/ reoxygenation (H/R)-induced cell damage. The results showed that chrysophanol prevented H/R-induced apoptosis via downregulation of cleaved Caspase-3, p-JNK, and Bax but upregulation of Bcl-2 expression. In contrast, chrysophanol attenuated H/R-induced endoplasmic reticulum (ER) stress via the downregulation of CHOP and p-IRE1α expression. Our data demonstrated that chrysophanol alleviated H/R-induced lipid ROS accumulation and ferroptosis. Therefore, we propose that chrysophanol may have a protective effect against AKI by regulating apoptosis, ER stress, and ferroptosis.

Poria cocos Regulates Cell Migration and Actin Filament Aggregation in B35 and C6 Cells by Modulating the RhoA, CDC42, and Rho Signaling Pathways.

Poria is used as a traditional Chinese herbal medicine with anti-inflammatory, anticancer, and mood-stabilizing properties. Poria contains triterpenoids and polysaccharides, which are reported to regulate the cytoplasmic free calcium associated with the N-methyl-D-aspartate receptor and affect the cell function of neonatal rat nerve cells and hippocampal neurons. Although the modulatory effects of Poria on neuronal function have been widely reported, the molecular mechanism of these effects is unclear. Cell migration ability and the reorganization of actin filaments are important biological functions during neuronal development, and they can be regulated mainly by the Rho signaling pathway. We found that the cell migration ability and actin condensation in B35 cells enhanced by P. cocos (a water solution of P. cocos cum Radix Pini (PRP) or White Poria (WP)) might be caused by increased RhoA and CDC42 activity and increased expression of downstream ROCK1, p-MLC2, N-WASP, and ARP2/3 in B35 cells. Similar modulations of cell migration ability, actin condensation, and Rho signaling pathway were also observed in the C6 glial cell line, except for the PRP-induced regulation of RhoA and CDC42 activities. Ketamine-induced inhibition of cell migration and actin condensation can be restored by P. cocos. In addition, we observed that the increased expression of RhoA and ROCK1 or the decreased expression of CDC42 and N-WASP caused by ketamine in B35 cells could also be restored by P. cocos. The results of this study suggest that the regulatory effects of P. cocos on cell migration and actin filament aggregation are closely related to the regulation of RhoA, CDC42, and Rho signaling pathways in both B35 and C6 cells. PRP and WP have the potential to restore neuronal cell Rho signaling abnormalities involved in some mental diseases.

Tournefortia sarmentosa Inhibits the Hydrogen Peroxide-Induced Death of H9c2 Cardiomyocytes.

Tournefortia sarmentosa is a traditional Chinese medicine used to reduce tissue swelling, to exert the antioxidant effect, and to detoxify tissue. T. sarmentosa is also used to promote development in children and treat heart dysfunction. However, many of the mechanisms underlying the effects of T. sarmentosa in the treatment of disease remain unexplored. In this study, we investigated the antioxidant effect of T. sarmentosa on rat H9c2 cardiomyocytes treated with hydrogen peroxide (H2O2). T. sarmentosa reduced the cell death induced by H2O2. T. sarmentosa inhibited H2O2-induced changes in cell morphology, activation of cell death-related caspases, and production of reactive oxygen species. In addition, we further analyzed the potential active components of T. sarmentosa and found that the compounds present in the T. sarmentosa extract, including caffeic acid, rosmarinic acid, salvianolic acid A, and salvianolic acid B, exert effects similar to those of the T. sarmentosa extract in inhibiting H2O2-induced H9c2 cell death. Therefore, according to the results of this study, the ability of the T. sarmentosa extract to treat heart disease may be related to its antioxidant activity and its ability to reduce the cellular damage caused by free radicals.

Safflower Extract Inhibits ADP-Induced Human Platelet Aggregation.

Safflower extract is commonly used as a traditional Chinese medicine to promote blood circulation and remove blood stasis. The antioxidant and anticancer properties of safflower extracts have been extensively studied, but their antiaggregative effects have been less analyzed. We found that safflower extract inhibited human platelet aggregation induced by ADP. In addition, we further analyzed several safflower extract compounds, such as hydroxysafflor yellow A, safflower yellow A, and luteolin, which have the same antiaggregative effect. In addition to analyzing the active components of the safflower extract, we also analyzed their roles in the ADP signaling pathways. Safflower extract can affect the activation of downstream conductors of ADP receptors (such as the production of calcium ions and cAMP), thereby affecting the expression of activated glycoproteins on the platelet membrane and inhibiting platelet aggregation. According to the results of this study, the effect of safflower extract on promoting blood circulation and removing blood stasis may be related to its direct inhibition of platelet activation.

Wild Bitter Melon Extract Regulates LPS-Induced Hepatic Stellate Cell Activation, Inflammation, Endoplasmic Reticulum Stress, and Ferroptosis.

The activation of hepatic stellate cells (HSCs) is a key component of liver fibrosis. Two antifibrosis pathways have been identified, the reversion to quiescent-type HSCs and the clearance of HSCs through apoptosis. Lipopolysaccharide- (LPS-) induced HSCs activation and proliferation have been associated with the development of liver fibrosis. We determined the pharmacological effects of wild bitter melon (WM) on HSC activation following LPS treatment and investigated whether WM treatment affected cell death pathways under LPS-treated conditions, including ferroptosis. WM treatment caused cell death, both with and without LPS treatment. WM treatment caused reactive oxygen species (ROS) accumulation without LPS treatment and reversed the decrease in lipid ROS production in HSCs after LPS treatment. We examined the effects of WM treatment on fibrosis, endoplasmic reticulum (ER) stress, inflammation, and ferroptosis in LPS-activated HSCs. The western blotting analysis revealed that the WM treatment of LPS-activated HSCs induced the downregulation of the connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), integrin-ß1, phospho-JNK (p-JNK), glutathione peroxidase 4 (GPX4), and cystine/glutamate transporter (SLC7A11) and the upregulation of CCAAT enhancer-binding protein homologous protein (CHOP). These results support WM as an antifibrotic agent that may represent a potential therapeutic solution for the management of liver fibrosis.

Acupuncture Point Stimulation Treatments Combined With Conventional Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD), which is a disease characterized by dyspnea, cough, and respiratory symptoms, leading to impaired health-related quality of life (HRQL) and exercise capacity, is highly prevalent worldwide. Some studies demonstrated that acupuncture point stimulation treatments (APSTs) are effective and safe in treating patients with COPD. The aim of this systematic review and network meta-analysis is to analyze the effects on HRQL and FEV1% predicted of diverse APSTs in treating patients with COPD. Materials and Methods: We searched seven electronic databases. Randomized controlled trials (RCTs) with stable COPD patients comparing APSTs and conventional treatment (Tx) were included. The primary outcome was HRQL measured by COPD Assessment Test or St. George's Respiratory Questionnaire. The secondary outcome was FEV1% predicted. We performed random effect network meta-analysis using a consistency model. Results: This network meta-analysis analyzed 21 RCTs with 1,577 stable COPD participants. In comparison with Tx, acupressure massage (AM) + Tx [-5.11; 95% confidence interval (CI), -6.65 to -3.57] was the most effective intervention in improving HRQL, followed by moxibustion (Mx) + Tx (-2.86; 95% CI, -3.86 to -1.86). Moreover, in comparison with Tx, Mx + Tx (7.79; 95% CI, 2.16 to 13.42) was the most effective intervention in improving FEV1% predicted, followed by acupuncture (A) + Tx (5.79; 95% CI, 2.90 to 8.68). Conclusions: Combined interventions (APSTs + Tx) are more effective than single intervention in improving both HRQL and FEV1% predicted. AM, Mx, and A can be considered effective non-pharmacological complementary interventions in treating patients with COPD under Tx.

An Apriori Algorithm-Based Association Rule Analysis to Identify Acupoint Combinations for Treating Diabetic Gastroparesis.

We explored the potential association rules within acupoints in treating diabetic gastroparesis (DGP) using Apriori algorithm complemented with another partition-based algorithm, a frequent pattern growth algorithm. Apriori algorithm is a data mining-based analysis that is widely applied in various fields, such as business and medicine, to mine frequent patterns in datasets. To search for effective acupoint combinations in the treatment of DGP, we implemented Apriori algorithm to investigate the association rules of acupoints among 17 randomized controlled trials (RCTs). The acupoints were extracted from the 17 included RCTs. In total, 29 distinct acupoints were observed in the RCTs. The top 10 frequently selected acupoints were CV12, ST36, PC6, ST25, BL21, BL20, BL23, SP6, BL18, and ST21. The frequency pattern of acupoints achieved by using a frequent pattern growth algorithm also confirms the result. The results showed that the most associated rules were {BL23, BL18} ≥ {SP6}, {BL20, BL18} ≥ {PC6}, {PC6, BL18} ≥ {BL20}, and {SP6, BL18} ≥ {BL23} in the database. Acupoints, including BL23, BL18, SP6, BL20, and PC6, can be deemed as core elements of acupoint combinations for treating DGP.

An Association Rule Analysis of Combined Acupoints for the Treatment of Patients with Dry Eye Disease.

BACKGROUND: Dry eye disease (DED) has a higher incidence in old age and is seen predominantly in females worldwide. Neurosensory abnormalities, ocular surface inflammation and damage, film instability, and hyperosmolarity are major and proven pathologies responsible for a poor quality of life. Tear breakup time and Schirmer's I test are predominantly used for the evaluation of primary outcomes in patients undergoing conventional treatment. A previous meta-analysis of some relevant studies proved that combination of acupoints could be more effective than single acupoint treatment. OBJECTIVES: The present study aimed to undertake association rule mining and examined the potential kernel acupoint combination in DED treatment constructed from the extracted randomized controlled trials (RCTs) based on a previous meta-analysis. METHODS: We summarized 32 acupoints as binary data from the 12 eligible RCTs and analyzed them based on the Apriori algorithm. RESULTS: TE23, BL2, ST2, ST1, EX-HN5, BL1, LI4, ST36, SP6, and KI3 were the 10 most frequently selected acupoints. The major associated rules in combination of acupoints were {TE23, LI4} ≥ {ST1} and {TE23, ST1} ≥ {LI4}, as inferred from 23 association rules. CONCLUSIONS: For acupuncture treatment of DED, combined TE23, LI4, and ST1 acupoints could be settled as the kernel of acupoint combination.

An Apriori Algorithm-Based Association Rule Analysis to Identify Herb Combinations for Treating Uremic Pruritus Using Chinese Herbal Bath Therapy.

Uremic pruritus (UP) is prevalent among patients with end-stage renal disease (ESRD), which causes severe itching and affects their quality of life. Additionally, patients experience fatigue and depression, and an increased risk of mortality has also been reported. A meta-analysis of 17 randomized controlled trials (RCTs) has indicated that Chinese herbal bath therapy (CHBT) had adjuvant benefits in improving UP in ESRD patients, and previous studies have reported that herb combinations were more useful than treatment with a single herb. Association rule analysis has been used to evaluate potential correlations between herb combinations, and Apriori algorithms are one of the most powerful machine-learning algorithms available for identifying associations within databases. Therefore, we used the Apriori algorithm to analyze association rules of potential core herb combinations for use in CHBT for UP treatment using data from a meta-analysis of 17 RCTs that used CHBT for UP treatment. Data on 43 CHBT herbs were extracted from 17 RCTs included for analysis and we found 19 association rules. The results indicated that the following herb combinations {Chuanxiong, Baijili} ≥ {Dahuang} and {Dahuang, Baijili} ≥ {Chuanxiong} were most strongly associated, implying that these herb combinations represent potential CHBT treatments for UP.

Role of Chrysophanol in Epithelial-Mesenchymal Transition in Oral Cancer Cell Lines via a Wnt-3-Dependent Pathway.

Oral cancer belongs to the group of head and neck cancers. If not diagnosed or treated early, it can be life threatening. Epithelial-mesenchymal transition (EMT) plays an important role in tumor formation and progression. An increase in the presence of the EMT phenotype causes tumor cell proliferation, migration, invasion, and poor prognosis. Therefore, attenuating carcinogenesis via EMT inhibition is a good strategy. Herein, we will determine the pharmacological effects of chrysophanol on the EMT in FaDu cells. To analyze EMT, we detected the expression EMT markers, including α-SMA, ß-catenin, vimentin, N-cadherin, E-cadherin, phospho-GSK-3ß, and nuclear translocations of p65 and ß-catenin by western blotting. Additionally, accumulating evidence indicates that reactive oxygen species (ROS) mediate EMT. Our results showed that the level of ROS was significantly increased after chrysophanol treatment. We further speculated that chrysophanol-mediated EMT and metastasis are involved in the Wnt-3-dependent signaling pathway. The inhibition of the EMT phenotype and metastasis and accumulation of ROS caused by chrysophanol was reversed by treatment with the Wnt-3 agonist Bml 284. Therefore, our findings indicated that chrysophanol altered EMT formation, ROS accumulation, and metastasis via the Wnt-3-dependent signaling pathway.

Therapeutic effects and mechanisms of actions of Descurainia sophia.

Descurainia sophia Webb ex Prantl has been used in traditional medicine globally. It has been shown that Descurainia sophia, together with many other bioactive compounds, can modulate the biological functions of various genes. We have viewed the clinical benefits and mechanisms of action of Descurainia sophia associated with its current uses and outlined potential further applications. There are many studies documenting its numerous clinical effects in cancer, respiratory, gastrointestinal, and cardiac systems. Further, Descurainia sophia has been shown to exhibit anti-inflammatory, anti-oxidative, and anthelmintic activities. The clinical studies did not indicate any significant adverse effects of Descurainia sophia, demonstrating that it is a safe and effective herbal medicine. However, more clinical studies demonstrating the therapeutic effects of Descurainia sophia are still warranted.

Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis.

Hepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing HBx and investigate whether chrysophanol (isolated from Rheum palmatum rhizomes) influences cell death via ferroptosis in vitro. Analysis of lipid reactive oxygen species (ROS), Bip, CHOP, p-IRE1α, GPX4, SLC7A11, α-SMA, and CTGF showed that chrysophanol attenuated HBx-repressed cell death. Chrysophanol can impair HBx-induced activation of HSCs via endoplasmic reticulum stress (ER stress) and ferroptosis-dependent and GPX4-independent pathways.

Chrysophanol Prevents Lipopolysaccharide-Induced Hepatic Stellate Cell Activation by Upregulating Apoptosis, Oxidative Stress, and the Unfolded Protein Response.

Hepatic stellate cell (HSC) activation is a vital driver of liver fibrosis. Recent research efforts have emphasized the clearance of activated HSCs by apoptosis, senescence, or reversion to the quiescent state. LPS induces human HSC activation directly and contributes to liver disease progression. Chrysophanol is an anthraquinone with hepatoprotective and anti-inflammatory effects. This study aimed to investigate the pharmacological effects and mechanisms of chrysophanol in an LPS-induced activated rat HSC cell line (HSC-T6). The fibrosis phenotype was identified from the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), and integrin ß1 by western blot analysis. We examined DNA fragmentation by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. We detected the apoptotic markers p53 and cleaved caspase-3 by western blot analysis. Intracellular ROS were labeled with 2',7'-dichlorofluorescein diacetate (DCF-DA) and the levels were measured by flow cytometry. Finally, we evaluated the ER stress markers binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) by Western blot analysis. Our results showed that chrysophanol decreased HSC-T6 cell viability in LPS-induced activated HSCs. Chrysophanol increased the expression of α-SMA, CTGF, integrin ßI, p53, cleaved caspase-3, and DNA fragmentation. Chrysophanol also elevated ROS levels and increased the expression of BiP and CHOP. Pretreatment with chrysophanol prevented LPS-induced HSC-T6 cell activation by upregulating apoptosis, ROS accumulation, unfolded protein response (UPR) activation, and the UPR proapoptotic effect.

Chrysophanol Regulates Cell Death, Metastasis, and Reactive Oxygen Species Production in Oral Cancer Cell Lines.

BACKGROUND: Oral cancer belongs to the class of head and neck cancers and can be life threatening if not diagnosed and treated early. Activation of cell death via apoptosis or reactive oxygen species (ROS) accumulation and inhibition of cell cycle progression, migration, and epithelial-to-mesenchymal transition (EMT) may be a good strategy to arrest the development of oral cancer. In this study, we analyzed the possible action of chrysophanol isolated from the rhizomes of Rheum palmatum on the oral cancer cell lines FaDu (human pharynx squamous cell carcinoma) and SAS (human tongue squamous carcinoma) by investigating whether chrysophanol could influence cell death. METHOD: Cell viability was measured by using the MTT assay. For the detection of apoptosis, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and subG1 population analysis were used. We also examined cell cycle progression and ROS levels by flow cytometry. Additionally, the expression of p53, p21, procaspase 3, cyclin D1, CDK4, cdc2, CDK2, E-cadherin, vimentin, and PCNA was evaluated by western blotting. CONCLUSION: Chrysophanol has an anticancer effect on FaDu and SAS cell lines. There is an increase in subG1 accumulation, ROS production, and cell cycle G1 arrest after treatment with chrysophanol. On the other hand, chrysophanol inhibited cell migration/metastasis and EMT. We proposed that chrysophanol may be a good candidate compound on oral cancer treatment in the further.