UPLC-Q-TOF-MS/MS-Based Targeted Discovery of Chetomin Analogues from Chaetomium cochliodes.

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.

Design, synthesis, and evaluation of n-butylphthalide and ligustrazine hybrids as potent neuroprotective agents for the treatment of ischemic stroke in vitro and in vivo.

A series of novel NBP-TMP hybrids with neuroprotective effects were designed and synthesized for the treatment of ischemic stroke. The anti-cerebral ischemic activity of these compounds was screened by evaluating their neuroprotective effects on the oxygen glucose deprivation/reperfusion (OGD/R)-induced SH-SY5Y cell injury model in vitro. Nine compounds 7e, 7h-7i, 7k, 7m-7p and 7r showed better activities on cell viability and LDH levels compared to NBP at the concentration of 6.25 µM. Among them, compound 7m showed the best potency with a percentage of protection 90.2 % compared to NBP (69.2 %) and other compounds. Preliminary structure-activity analysis revealed that the introduction of iodine and N-methylpiperazine groups could significantly improve the neuroprotective effect. Further mechanism research showed that compound 7m could reduce the damage to neuronal mitochondria caused by OGD/R by reducing ROS and increasing mitochondrial membrane potential (MMP), and reduce the apoptosis and necrosis of neurons to play a neuroprotective role. In addition, 7m could regulate the levels of mitochondrial apoptosis pathway-related proteins Bcl-2, Bax, and caspase 3. Finally, in vivo experiments showed that the compound 7m significantly inhibited ischemia-reperfusion injury and cerebral blood flow in rats, and showed a more significant neuroprotective effect than the positive drug NBP at a dose concentration of 20 mg/kg. In conclusion, our results suggest that 7m may be used as a novel lead compound for the future development of anti-cerebral ischemic agents.

Trading-Off Transit and Non-Transit Physical Activity among Older People: Evidence from Longitudinal Accelerometer Data of a Natural Experiment Study.

This study used a natural experiment of a new metro line in Hong Kong to examine trade-offs between transit-related and non-transit-related physical activity (PA) among 104 older people (aged ≥ 65 years) based on longitudinal accelerometer data that distinguished transit-related and non-transit-related PA. Difference-in-difference (DID) analysis compared PA changes between treatment and control groups. We found that new metro stations have trade-off effects between transit and non-transit PA. After opening metro stations, transit-related PA increased by 12 min per day on average, but non-transit-related PA decreased by 18 min per day. In addition, the proportion of time spent in transit-related PA increased by 6%. The results suggested that new metro stations could generate transit-related PA, but it might shift from non-transit-related PA among older people. Our findings revealed trade-off effects of public transit interventions and have significant implications for transport and healthy ageing studies.

Ginsenoside Rg3 Protects against Diabetic Cardiomyopathy and Promotes Adiponectin Signaling via Activation of PPAR-γ.

Ginsenoside Rg3 extracted from Panax notoginseng has therapeutic effects on diabetes and heart diseases. However, the underlying mechanism of ginsenoside Rg3 on diabetic cardiomyopathy (DCM) remains unclear. 24-week-old diabetic db/db mice were treated with ginsenoside Rg3 for 12 weeks, then body weight, serum lipids, adiponectin levels, as well as cardiac function and pathological morphology, were measured. The targets of ginsenoside Rg3 and its regulation of the adiponectin pathway were also evaluated on 3T3-L1 or H9c2 cells. Ginsenoside Rg3 directly bound to PPAR-γ, improving adiponectin secretion and promoting adiponectin signaling. Significantly attenuated overweight, hyperglycemia, and hyperlipidemia, as well as alleviated lipid accumulation and dysfunction in adipose, liver, and heart tissues, were observed in the ginsenoside Rg3-treated group. Ginsenoside Rg3 could be a promising drug targeting PPAR-γ to treat diabetic cardiomyopathy.

Role of glycolysis in the development of atherosclerosis.

Atherosclerosis is a chronic inflammatory vascular disease associated with endothelial dysfunction, inflammation, and atherosclerotic plaque formation. Glycolysis is a conservative and rigorous biological process that decomposes glucose into pyruvate. Its function is to provide the body with energy and intermediate products required for life activities. However, abnormalities in glycolysis flux during the progression of atherosclerosis accelerate the disease progression. Herein, we review the role of glycolysis in the development of atherosclerosis to provide new ideas for devising novel antiatherosclerosis strategies.

Decline in older adults' daily mobility during the COVID-19 pandemic: the role of individual and built environment factors.

BACKGROUND: Extensive research has shown that the COVID-19 pandemic dramatically impacted the daily mobility of older adults. However, very little attention has been paid to the role of individual and built environmental factors in decline in older adults' daily mobility during the pandemic. METHODS: Based on a cohort survey of 741 older adults in Hong Kong, we conducted a one-way ANOVA to explore the differences in determinants (individual or environmental factors) of older adults' daily mobility between before and during the COVID-19 pandemic. Further, multilevel linear regression was performed to examine how individual characteristics and built environment factors are associated with changes in older adults' daily mobility during the pandemic. RESULTS: Results show that the duration of active travel declined from 174.72 to 76.92 min per week, and that the public transport use frequency decreased from an average of 6.14 to 3.96 trips per week during the COVID-19 pandemic (before the rollout of vaccination programme). We also found residential density (p < 0.05) and the number of bus stop was negatively associated with the decline in their active travel (p < 0.01), while a higher destination mix was associated with more significant decrease in active travel (p < 0.01). A higher availability of recreational facilities in neighbourhoods was associated with a greater decrease in public transport use (p < 0.05). In addition, those who were older or having depressive symptoms, which are considered a vulnerable group, were negatively associated with decrease in their mobility (p < 0.001). CONCLUSIONS: Maintaining mobility and social interactions are crucial for older adults' health during the COVID-19 pandemic. This study found that individual and environmental factors differentially affected older adults' active travel and public transport use during the pandemic. Our findings contribute to understanding the COVID-19 impact on daily mobility in older adults and support more effective active travel promotion policies in the post-pandemic future.

Role of Adiponectin in Cardiovascular Diseases Related to Glucose and Lipid Metabolism Disorders.

Lifestyle changes have led to increased incidence of cardiovascular disease (CVD); therefore, potential targets against CVD should be explored to mitigate its risks. Adiponectin (APN), an adipokine secreted by adipose tissue, has numerous beneficial effects against CVD related to glucose and lipid metabolism disorders, including regulation of glucose and lipid metabolism, increasing insulin sensitivity, reduction of oxidative stress and inflammation, protection of myocardial cells, and improvement in endothelial cell function. These effects demonstrate the anti-atherosclerotic and antihypertensive properties of APN, which could aid in improving myocardial hypertrophy, and reducing myocardial ischemia/reperfusion (MI/R) injury and myocardial infarction. APN can also be used for diagnosing and predicting heart failure. This review summarizes and discusses the role of APN in the treatment of CVD related to glucose and lipid metabolism disorders, and explores future APN research directions and clinical application prospects. Future studies should elucidate the signaling pathway network of APN cardiovascular protective effects, which will facilitate clinical trials targeting APN for CVD treatment in a clinical setting.

Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) protects against focal cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

CONTEXT: Folium Ginkgo extract and tetramethylpyrazine sodium chloride injection (Xingxiong injection) is a compound preparation commonly used for treating cerebral ischaemia/reperfusion injury in ischaemic stroke in China. However, its potential mechanisms on ischaemic stroke remain unknown. OBJECTIVE: This study explores the potential mechanisms of Xingxiong injection in vivo or in vitro. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly assigned to five groups: the sham (normal saline), the model (normal saline) and the Xingxiong injection groups (12.5, 25 or 50 mL/kg). The rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 14 d. Xingxiong injection was administered via intraperitoneal (i.p.) injection immediately after ischaemia induction for 14 d. Afterwards, rats were sacrificed at 14 d induced by administration of Xingxiong injection. RESULTS: Xingxiong injection significantly reduces infarct volume (23%) and neurological deficit scores (93%) compared with the MCAO/R group. Additionally, Xingxiong injection inhibits the loss in mitochondrial membrane potential (43%) and reduces caspase-3 level (44%), decreases NOX (41%), protein carbonyl (29%), 4-HNE (40%) and 8-OhdG (41%) levels, inhibits the expression of inflammatory factors, such as TNF-α (26%), IL-1ß (34%), IL-6 (39%), MCP-1 (36%), CD11a (41%) and ICAM-1 (43%). Moreover, Xingxiong injection can increase p-Akt/Akt (35%) and Nrf2 (47%) protein expression and inhibit NLRP3 (42%) protein expression. CONCLUSIONS: Xingxiong injection prevents cerebral ischaemia/reperfusion injury via activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome. These findings provide experimental evidence for clinical use of drugs in the treatment of ischaemic stroke.

[Research progress on pharmacology of butylphthalide and its derivatives].

The butylphthalide(NBP), a colorless or light yellow viscous oily component isolated from celery seeds, has the effects of anti-inflammation, anti-oxidative stress, protecting blood-brain barrier, improving cerebral microcirculation, and promoting angiogenesis. It can protect the neurological function of patients with ischemic stroke through a variety of mechanisms, improve the symptoms of patients, and contribute to the long-term recovery of them. Therefore, independently developed in China, NBP was approved by State Food and Drug Administration for the clinical treatment of stroke patients in 2002. At the same time, owing to the complex multi-target pharmacological mechanism, NBP has been frequently used in clinical practice. As frequently verified, it has obvious effects in the treatment of other neurological diseases such as Alzheimer's disease, vascular dementia, Parkinson's disease, autoimmune diseases, depression, traumatic central nervous system injury. Moreover, it demonstrates significant pharmacological effects on non-neurological diseases such as diabetes mellitus and myocardial infarction. Therefore, this study summarizes the research progress on roles of NBP in nervous system diseases and non-nervous system diseases, and the pharmacological characteristics and mechanisms of NBP, which is expected to lay a basis for research on related targets.

Berberine Improves the Protective Effects of Metformin on Diabetic Nephropathy in db/db Mice through Trib1-dependent Inhibiting Inflammation.

PURPOSE: Diabetic nephropathy (DN), one of severe diabetic complications in the diabetes, is the main cause of end stage renal disease (ESRD). Notably, the currently available medications used to treat DN remain limited. Here, we determined whether berberine (BBR) could enhance the anti-diabetic nephropathy activities of metformin (Met) and explored its possible mechanisms. METHOD: The anti-diabetic nephropathy properties were systematically analyzed in the diabetic db/db mice treated with Met, BBR or with combination of Met and BBR. RESULTS: We found that both single Met and BBR treatments, and combination therapy could lower blood glucose, and ameliorate insulin resistance. The improvement of lipids metabolism by co-administration was more evident, as indicated by reduced serum cholesterol and less fat accumulation in the liver. Further, it was found that Met and BBR treatments, and co-administration could attenuate the progression of DN. However, anti-diabetic nephropathy activities of Met were enhanced when combined with BBR, as evidenced by improved renal function and histological abnormalities of diabetic kidney. Mechanistically, BBR enhanced renal-protective effects of Met primarily through potently promoting expression of Trib1, which subsequently downregulated the increased protein levels of CCAAT/enhancer binding protein α (C/EBPα), and eventually inhibited fatty synthesis proteins and nuclear factor kappa-B (NF-κB) signaling. CONCLUSION: Our data provide novel insight that co-administration of BBR and Met exerts a preferable activity of anti-diabetic nephropathy via collectively enhancing lipolysis and inhibiting inflammation. Combination therapy with these two drugs may provide an effective therapeutic strategy for the medical treatment of diabetic nephropathy.

Paclobutrazol exposure induces apoptosis and impairs autophagy in hepatocytes via the AMPK/mTOR signaling pathway.

Paclobutrazol (PBZ), one of the most widely used plant growth retardants in vegetables, fruits, and traditional Chinese medicine ingredients, exposes people to adverse events. In this study, HepaRG hepatocytes were cultured and exposed to PBZ (360 µM) in vitro to determine its mechanism. Results showed that PBZ exposure inhibited cell viability in a time- and dose-dependent manner and increased the oxidative stress and apoptosis ratio in HepaRG cells. These data revealed that the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) has an important role in PBZ-induced cell apoptosis, which is mediated by impaired autophagy and blocked by the AMPK activator. In conclusion, PBZ exposure induces apoptosis and impairs autophagy in hepatocytes via the AMPK/mTOR signaling pathway.

[Effect of Guanxin Danshen Formulation on diabetic kidney disease in db/db mice through regulation of Nrf2 pathway].

Diabetic kidney disease(DKD) has become a primary cause of end-stage kidney disease, without any effective treatment available. In this study, we assessed the protective effect of Guanxin Danshen Formulation(GXDSF) on diabetic nephropathy in db/db mice. The db/m and db/db mice were randomly divided into 4 groups: control group, model group, metformin group, and GXDSF group. After 8 weeks' treatment with GXDSF, metformin or normal saline, the mice were sacrificed, and the blood and kidney tissues were collected for the further analysis. Compared with the model group, TG, TCH and LDL levels significantly decreased in the GXDSF group. The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume, basement-membrane thickening and mesangial cell proliferation, which could be significantly alleviated by GXDSF treatment. GXDSF treatment also reduced serum creatinine and BUN. Meanwhile, GXDSF treatment markedly elevated GSH-PX levels, while reduced LDH and MDA levels in the kidney tissues. Western blot assay showed that GXDSF evidently up-regulated protein levels of ERα and p-Akt, and subsequently promoted HO-1 expression mediated by Nrf2. These data collectively indicated that GXDSF protects db/db mice against DN by regulating ERα and Nrf2-mediated HO-1 expression.

Ginsenoside Rb1 and mitochondria: A short review of the literature.

Mitochondria play a central role in various critical cellular processes, including energy synthesis, energy supply and apoptosis. Panax notoginseng, a commonly used traditional Chinese medicine, has various pharmacological effects on the human body. Ginsenosides are representative bioactive components of P. notoginseng. Recently, more attention has focused on ginsenoside Rb1 as an antioxidative and anti-inflammatory agent that can protect the nervous system and the cardiovascular system. Numerous studies have shown that Rb1 exerts these effects by regulating mitochondrial energy metabolism, mitochondrial fission and fusion, apoptosis, oxidative stress and reactive oxygen species release, mitophagy and mitochondrial membrane potential. Thus, the mitochondria are pivotal targets of Rb1. This review summarized the available reports of the effects of ginsenoside Rb1 on the regulation of mitochondria and showed that it has a promising role in treating mitochondrial diseases.

Ginsenoside Rb1 mitigates oxidative stress and apoptosis induced by methylglyoxal in SH-SY5Y cells via the PI3K/Akt pathway.

Diabetic encephalopathy is a severe diabetic complication characterized by cognitive dysfunction and neuropsychiatric disability. Methylglyoxal (MGO), a highly reactive metabolite of hyperglycemia, serves as a major precursor of advanced glycation end products that play key roles in diabetic complications. Ginsenoside Rb1 (abbreviated as Rb1) has received extensive attention due to its potential therapeutic effects on diabetes and neurodegeneration. Therefore, this study aimed to investigate the effects of Rb1 on MGO-induced damage in SH-SY5Y cells and the related mechanism. SH-SY5Y cells were pretreated with Rb1 for 8 h and then exposed to MGO (0.5 mM) for 24 h. Cell survival was assessed by the MTT assay. Cell apoptosis was assessed using Hoechst 33342/propidium iodide (PI) staining and an Annexin-V/PI kit. The activities of oxidative stress markers were examined using commercial kits. Reactive oxygen species (ROS) staining and JC-1 staining were used to evaluate mitochondria injury. In addition, protein levels were measured by Western blot analysis. As a result, Rb1 alleviated the injury induced by MGO by increasing the activities of superoxide dismutase, catalase and total glutathione, decreasing the level of malondialdehyde, and alleviating mitochondrial damage and ROS production. Furthermore, Rb1 could enhance the Bcl-2/Bax ratio, inhibit the expression of cleaved caspase-3 and cleaved caspase-9, and enhance the levels of phosphorylated Akt. Moreover, the protective effects of Rb1 against MGO-induced apoptosis were partly abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation. Our results demonstrated that Rb1 ameliorated MGO-induced oxidative stress and apoptosis in SH-SY5Y cells via activating the PI3K/Akt signaling pathway.

SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata (Miq) Seem against high-fat diet-induced atherosclerosis in ApoE-/- mice.

Total aralosides of Aralia elata (Miq) Seem (TASAESs) possess multiple pharmacological activity, such as anti-inflammation, antioxidation, and antiapoptosis. However, there is no literature reporting the antiatherosclerotic effect and mechanism of TASAES so far. The aim of this study was to investigate the antiatherosclerotic effects in high-fat diet-induced ApoE-/- mice and potential mechanism of TASAES in ox-LDL-injured endothelial cells. In vivo assay, our data demonstrated that TASAES significantly reduced the atherosclerotic plaque size and caspase-3 expression level in aortic valve. In vitro, we found that TASAES could increase endothelial cell viability, attenuated mitochondrial membrane potential depolarization, and endothelial cells apoptosis. In addition, we found that TASAES could activate SIRT1/AMPK and Akt/eNOS signaling pathways. Importantly, EX527, SIRT1 siRNA, and LY294002, Akt siRNA, remarkably abolished the antiapoptotic effects of TASAES. In conclusion, this study demonstrated that SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of TASAES against atherosclerotic mice, suggesting that TASAES is a candidate drug for atherosclerosis treatment.

An In Silico Model for Predicting Drug-Induced Hepatotoxicity.

As one of the leading causes of drug failure in clinical trials, drug-induced liver injury (DILI) seriously impeded the development of new drugs. Assessing the DILI risk of drug candidates in advance has been considered as an effective strategy to decrease the rate of attrition in drug discovery. Recently, there have been continuous attempts in the prediction of DILI. However, it indeed remains a huge challenge to predict DILI successfully. There is an urgent need to develop a quantitative structure-activity relationship (QSAR) model for predicting DILI with satisfactory performance. In this work, we reported a high-quality QSAR model for predicting the DILI risk of xenobiotics by incorporating the use of eight effective classifiers and molecular descriptors provided by Marvin. In model development, a large-scale and diverse dataset consisting of 1254 compounds for DILI was built through a comprehensive literature retrieval. The optimal model was attained by an ensemble method, averaging the probabilities from eight classifiers, with accuracy (ACC) of 0.783, sensitivity (SE) of 0.818, specificity (SP) of 0.748, and area under the receiver operating characteristic curve (AUC) of 0.859. For further validation, three external test sets and a large negative dataset were utilized. Consequently, both the internal and external validation indicated that our model outperformed prior studies significantly. Data provided by the current study will also be a valuable source for modeling/data mining in the future.

Herb-Induced Liver Injury: Phylogenetic Relationship, Structure-Toxicity Relationship, and Herb-Ingredient Network Analysis.

Currently, hundreds of herbal products with potential hepatotoxicity were available in the literature. A comprehensive summary and analysis focused on these potential hepatotoxic herbal products may assist in understanding herb-induced liver injury (HILI). In this work, we collected 335 hepatotoxic medicinal plants, 296 hepatotoxic ingredients, and 584 hepatoprotective ingredients through a systematic literature retrieval. Then we analyzed these data from the perspectives of phylogenetic relationship and structure-toxicity relationship. Phylogenetic analysis indicated that hepatotoxic medicinal plants tended to have a closer taxonomic relationship. By investigating the structures of the hepatotoxic ingredients, we found that alkaloids and terpenoids were the two major groups of hepatotoxicity. We also identified eight major skeletons of hepatotoxicity and reviewed their hepatotoxic mechanisms. Additionally, 15 structural alerts (SAs) for hepatotoxicity were identified based on SARpy software. These SAs will help to estimate the hepatotoxic risk of ingredients from herbs. Finally, a herb-ingredient network was constructed by integrating multiple datasets, which will assist to identify the hepatotoxic ingredients of herb/herb-formula quickly. In summary, a systemic analysis focused on HILI was conducted which will not only assist to identify the toxic molecular basis of hepatotoxic herbs but also contribute to decipher the mechanisms of HILI.

Notoginsenoside R1 Protects db/db Mice against Diabetic Nephropathy via Upregulation of Nrf2-Mediated HO-1 Expression.

Diabetic nephropathy (DN) is a leading cause of end-stage renal failure, and no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng, and our previous studies showed the cardioprotective and neuroprotective effects of NGR1. However, its role in protecting against DN remains unexplored. Herein, we established an experimental model in db/db mice and HK-2 cells exposed to advanced glycation end products (AGEs). The in vivo investigation showed that NGR1 treatment increased serum lipid, ß2-microglobulin, serum creatinine, and blood urea nitrogen levels of db/db mice. NGR1 attenuated histological abnormalities of kidney, as evidenced by reducing the glomerular volume and fibrosis in diabetic kidneys. In vitro, NGR1 treatment was further found to decrease AGE-induced mitochondria injury, limit an increase in reactive oxygen species (ROS), and reduce apoptosis in HK-2 cells. Mechanistically, NGR1 promoted nucleus nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions to eliminate ROS that induced apoptosis and transforming growth factor beta (TGF-ß) signaling. In summary, these observations demonstrate that NGR1 exerts renoprotective effects against DN through the inhibition of apoptosis and renal fibrosis caused by oxidative stress. NGR1 might be a potential therapeutic medicine for the treatment of DN.

Interspecies Variation in NCMN-O-Demethylation in Liver Microsomes from Various Species.

NCMN (N-(3-carboxy propyl)-4-methoxy-1,8-naphthalimide), a newly developed ratiometric two-photon fluorescent probe for human Cytochrome P450 1A (CYP1A), shows the best combination of specificity and reactivity for real-time detection of the enzymatic activities of CYP1A in complex biological systems. This study aimed to investigate the interspecies variation in NCMN-O-demethylation in commercially available liver microsomes from human, mouse, rat, beagle dog, minipig and cynomolgus monkey. Metabolite profiling demonstrated that NCMN could be O-demethylated in liver microsomes from all species but the reaction rate varied considerably. CYP1A was the major isoform involved in NCMN-O-demethylation in all examined liver microsomes based on the chemical inhibition assays. Furafylline, a specific inhibitor of mammalian CYP1A, displayed differential inhibitory effects on NCMN-O-demethylation in all tested species. Kinetic analyses demonstrated that NCMN-O-demethylation in liver microsomes form rat, minipig and cynomolgus monkey followed biphasic kinetics, while in liver microsomes form human, mouse and beagle dog obeyed Michaelis-Menten kinetics, the kinetic parameters from various species are much varied, while NCMN-O-demethylation in MLM exhibited the highest similarity of specificity, kinetic behavior and intrinsic clearance as that in HLM. These findings will be very helpful for the rational use of NCMN as a practical tool to decipher the functions of mammalian CYP1A or to study CYP1A associated drug-drug interactions in vivo.

The Cardiotoxicity Induced by Arsenic Trioxide is Alleviated by Salvianolic Acid A via Maintaining Calcium Homeostasis and Inhibiting Endoplasmic Reticulum Stress.

Arsenic trioxide (ATO) has been verified as a breakthrough with respect to the management of acute promyelocytic leukemia (APL) in recent decades but associated with some serious adverse phenomena, particularly cardiac functional abnormalities. Salvianolic acid A (Sal A) is a major effective component in treating ATO-induced cardiotoxicity. Therefore, the objective of our study was to assess whether Sal A had protective effects by the regulation of calcium homeostasis and endoplasmic reticulum (ER) stress. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A via daily tail vein injections for two weeks. For the in vitro study, we detected the effects of ATO and/or Sal A in real time using adult rat ventricular myocytes (ARVMs) and an IonOptix MyoCam system. Our results showed that Sal A pretreatment alleviated cardiac dysfunction and Ca2+ overload induced by ATO in vivo and vitro. Moreover, Sal A increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity and expression, alleviated [Ca2+]ER depletion, and decreased ER stress-related protein expression. Sal A protects the heart from ATO-induced injury and its administration correlates with the modulation of SERCA, the recovery of Ca2+ homeostasis, and the down-regulation of ER stress-mediated apoptosis.