Zhihao Liu

• PhD
• Research Chemist at United States Department of Agriculture

Background: Hepatic transporters, including efflux transporters and uptake transporters, have been recognized to play an important role in the disposition of various drugs. These membrane transporters show extensive substrate specificity with an abundance of overlap, implying the probability of transporter involved in the drug-drug interactions wi...

Most drug products on the global pharmaceutical market are administered orally. The absorption of oral drug in the intestine is an important factor to determine the drug bioavailability. There are many intestinal transporters expressed on the small intestine and the transporters can be classified into two major families, SLC family and ABC family....

Vegetables from the Brassica family are rich in many health-beneficial components, including high levels of polyphenols and glucosinolates (GSLs). However, their exact metabolite compositions are highly affected by cultivating and environmental conditions. Here, we provide the first report of polyphenol and GSL composition of kale and broccoli micr...

Betulinic acid (BA) and 23-Hydroxybetulinic acid (23-HBA) are natural products with similar structures, which show a range of biological effects including cytotoxicity activity. The aim of current research was to investigate and evaluate the combinational cytotoxicity of BA and 23-HBA with chemotherapeutic agents in vitro, and to clarify the potent...

Enzymatic browning negatively impacts product quality and shelf-life of packaged fresh-cut lettuce. Metabolite profiles of lettuce are affected by the browning process. The purpose of this study was to identify metabolomic marker compounds to predict lettuce browning, which could be applied to discern accessions suited for commercial production and...

This study evaluated the fruits of Forsythia suspensa (Lianqiao), an important economic crop, for the chemical components of its water and ethanol extracts, inhibitory effects on SARS-CoV-2 virus spike protein binding to ACE2, inhibition of ACE2 activity, and capacity to scavenge free radicals. A total of 42 compounds were tentatively identified in...

Turmeric (Curcuma longa L.) is a perennial tuberous plant from the genus Curcuma (Zingiberaceae) and has been widely used in foods for thousands of years. The present study examined the ethanol extract of turmeric for its chemical composition, antimicrobial activity, and free radical scavenging properties. UHPLC-MS/MS analysis tentatively identifie...

The water and ethanol extracts of huangqin, the roots of Scutellaria baicalensis Georgi. with potential antiviral properties and antioxidant activities, were investigated for their chemical profiles and their abilities to interfere with the interaction between SARS-CoV-2 spike protein and ACE2, inhibiting ACE2 activity and scavenging free radicals....

Forsythia suspensa (Lianqiao) has long been touted for its anti-viral effects in folklore. Although promising, limited research were conducted to evaluate its potential in defending the severe acute respiratory syndrome coronavirus (SARS-CoV-2). This study evaluated the fruits of Forsythia suspensa (Lianqiao), an important economic crop, for the ch...

Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six com...

Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential i...

American ginseng (Panax quinquefolius L.) has been recognized as a valuable herb medicine, and ginsenosides are the most important components responsible for the health-beneficial effects. This study investigated the secondary metabolites responsible for the differentiation of wild and cultivated American ginsengs with ultrahigh-performance liquid...

COVID-19 is initiated by binding the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) on host cells. Food factors capable of suppressing the binding between the SARS-CoV-2 spike protein and ACE2 or reducing the ACE2 availability through ACE2 inhibitions may potentially reduce the risk of SARS-CoV-2 infection and COVID-19. In this...

This study aimed to investigate the effects of different thermal treatments (steaming and baking) on the chemical compositions, total content of antioxidant components, and the antioxidant properties of soluble-free, soluble-conjugated, and insoluble-bound phenolics from tomato seeds. Total phenolic content (TPC) and free radical scavenging activit...

Mass spectrometry (MS)-based techniques have been extensively applied in food and agricultural research. This review aims to address the advances and applications of MS-based analytical strategies in nontargeted and targeted analysis and summarizes the recent publications of MS-based techniques, including flow injection MS fingerprinting, chromatog...

The imidazo[1,2-a]pyridine-3-carboxyamides (IAPs) are a unique class of compounds endowed with impressive nanomolar in vitro potency against Mycobacterium tuberculosis (Mtb) as exemplified by clinical candidate Telacebec (Q203). These compounds target mycobacterial respiration through inhibition of the QcrB subunit of cytochrome bc1:aa3 super compl...

The soluble free, soluble conjugated, and insoluble bound phenolic compounds in tomato seeds were extracted and analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Total phenolic content (TPC) and free radical scavenging activities along with the antiproliferative effects against the human colorectal cance...

Intestinal ischemia-reperfusion (I/R) may induce cell/tissue injuries, leading to multiple organ failure. Based on our preexperiments, we proposed that sesamin could protect against and ameliorate intestinal I/R injuries and related disorders with involvement of activating Nrf2 signaling pathway. This proposal was evaluated using SD intestinal I/R...

The aim of this study was to characterize and reveal the protective effects of cinnamaldehyde (CA) against mesenteric ischemia-reperfusion- (I/R-) induced lung and liver injuries and the related mechanisms. Sprague-Dawley (SPD) rats were pretreated for three days with 10 or 40 mg/kg/d, ig of CA, and then induced with mesenteric ischemia for 1 h and...

In the present study, urine samples were collected from healthy human volunteers to determine the metabolic fates of phenolic compounds and glucosinolates after a single meal of kale and daikon radish. The major glucosinolates and phenolic compounds in kale and daikon radish were measured. The urinary metabolome after feeding at different time peri...

Background and Purpose Catalpol, a water‐soluble active ingredient isolated from Rehmannia glutinosa, exhibits multiple pharmacological activities. However, the mechanism(s) underlying protection against renal injury by catalpol remains unknown. Experimental Approach Adriamycin‐induced kidney injury models associated with podocyte damage were empl...

The aim of this study was to explore whether rhein could enhance the effects of pemetrexed (PTX) on the therapy of non‐small‐cell lung cancer (NSCLC) and to clarify the associated molecular mechanism. Our study shows that rhein in combination with PTX could obviously increase the systemic exposure of PTX in rats, which would be mediated by the inhi...

Estrogen-induced cholestasis is a common etiology of hepatic diseases in women with contraceptives administration, pregnancy or hormone replacement therapy. Farnesoid X receptor (FXR) is a member of nuclear receptor super family of ligand-activated transcription factors that is highly expressed in liver. FXR is acknowledged to contribute to the bil...

A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC 50 = 5.17 nM) and 7f (IC 50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). In particular, compound 7a als...

Hyperhomocysteinemia (HHCY) has been recognized as an independent risk factor for atherosclerosis and plays a vital role in the development of atherosclerosis. Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa, can produce anti-inflammatory, anti-oxidant, anti-tumor, and dopaminergic neurons protecting effects. This stud...

Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were...

To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam, renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats. A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different condit...

This study aimed to clarify that organic anion transporters (OATs) mediate the drug–drug interaction (DDI) between imipenem and cilastatin. After co-administration with imipenem, the plasma concentrations and the plasma concentration-time curve (AUC) of cilastatin were significantly increased, while renal clearance and cumulative urinary excretion...

Background/Aims: The emergence of multidrug resistance (MDR) caused by P-glycoprotein (P-gp) overexpression is a serious obstacle to the treatment of chronic myelocytic leukemia. In recent years, some clinical trials have shown that nelfinavir (NFV), a traditional anti-HIV drug, has anti-cancer effects. Some researchers have also shown NFV might be...

Topical application of trans-resveratrol was limited due to its insolubility and instability problems. In this work, three kinds of essential oil based microemulsions containing rose oil (RO-ME), jasmine oil (JO-ME) and lemon oil (LO-ME) were prepared, constituted of Cremophor EL/1,2-propanediol/essential oils (47: 23: 30, w/w). All the three micro...

Glucocorticoid‐induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO...

Backgroud Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. Dyslipidemia, pathoglycemia and insulin resistance are the major risk factors for the development of NAFLD. To date, no effective drug therapies for this condition have been approved. Purpose The present study was to investigate th...

Though the advancement of chemotherapy drugs alleviates the progress of cancer, long‐term therapy with anticancer agents gradually leads to acquired multidrug resistance (MDR), which limits the survival outcomes in patients. It was shown that dihydromyricetin (DMY) could partly reverse MDR by suppressing P‐glycoprotein (P‐gp) and soluble resistance...

The application of iodinated contrast medium has become a risk factor for metformin-associated lactic acidosis (MALA), which leads to the accumulation of metformin in vivo is one of the principal reasons for MALA. However, the molecular mechanism of the adverse event is not yet clear. In this study, iohexol injection was used as a model drug. The c...

Objectives Acute kidney injury (AKI) was a common organ damage that often occurred after cisplatin. This study was aimed at investigating the pharmacokinetic changes of cefdinir and cefditoren in AKI rats, and elucidating the possible molecular mechanisms. Methods The renal injury model was established by intraperitoneal injection of cisplatin (12...

A new class of thiodiphenylpyrimidine analogues (Thio‐DPPY) were synthesized as potent and selective EGFR T790M inhibitors to overcome gefitinib resistance in non‐small cell lung cancer (NSCLC). This structural optimization led to the identification of two potent EGFRT790M/L858R inhibitors, 14a and 14e, which possess IC50 values of 27.5 and 9.1 nM,...

Oxidative stress and inflammatory response are well known to be involved in the pathogenesis of acute liver injury. This study was performed to examine the hepatoprotective effect of ginsenoside Rg1 (Rg1) against CCl4‐induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway in vivo and in vitro. Mice were orall...

A new family of diphenylpyrimidine derivatives bearing an amino acid substituent were identified as potent BTK inhibitors. Among them, compound 7b, which features an l-proline substituent, was identified as the strongest BTK inhibitor, with an IC50 of 8.7 nM. Compound 7b also displayed similar activity against B-cell lymphoma cell lines as ibrutini...

The purpose of this study was to investigate the protective effect of rhein, a major metabolite of diacerein, on methotrexate (MTX)-induced hepatotoxicity and clarify the pharmacological mechanism. Rhein significantly reduced the elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by MTX in rat serum and improved...

Catalpol, an iridoid glucoside, has been found present in large quantities in the root of Rehmannia glutinosa L. and showed a strong antioxidant capacity in the previous study. In the present work, the protective effect of catalpol against AS via inhibiting oxidative stress, DNA damage, and telomere shortening was found in LDLr −/− mice. This study...

Figure S1: effects of catalpol or oxLDL on cell viability and catalpol-induced protective effects on oxidative stress in oxLDL-treated macrophages. Figure S2: catalpol-induced effects on cell DNA oxidative damage, apoptosis, and DNA damage in oxLDL-treated macrophages. Figure S3: effects of catalpol on DNA oxidative damage, apoptosis, DNA damage, a...

Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular...

The regulation of renal transporters such as organic anion transporter (OATs) is a new target for treatment of acute renal failure. The purpose of this study was to investigate whether the effect of puerarin (Pur) on renal damage induced by methotrexate (MTX) is related to the expression of renal Oat1/3 in vivo and in vitro, and to explore the rela...

This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MC...

Hepatic fibrosis is a pathological process that eventually leads to development of cirrhosis and liver cancer by various types of chronic liver disease. Up to date, there is no standard treatment for the progression of liver fibrosis. This study aims to investigate the hepatoprotection of auraptene (AUR), a simple coumarin contained in the peels of...

A multifunctional nanoparticulate system composed of methoxy poly(ethylene glycol)-poly(L-histidine)-d-α-Vitamin E succinate (MPEG-PLH-VES) copolymers for encapsulation of doxorubicin (DOX) was elaborated with the aim of circumventing the multidrug resistance (MDR) in breast cancer treatment. The MPEG-PLH-VES nanoparticles (NPs) were subsequently f...

Cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a newly therapeutic strategy against cholest...

Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in th...

A new class of acrylamide-substituted quinazoline derivatives with enhanced inhibitory activity against mutant EGFR T790M enzyme were synthesized. Among them, compound 10b displayed the strongest inhibitory potency to block the phosphorylation of the EGFR T790M enzyme, with an IC50value of 4.3 nM. Compared with the lead compound gefitinib, compound...

This study aimed to demonstrate that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between piperacillin and tazobactam. After co-administration with piperacillin in rats, the AUC of tazobactam in plasma was significantly increased, and t1/2β was prolonged with significant reduction in plasma clearance, renal clearance an...

Type 2 diabetes is characterized by insulin resistance in target tissues and hyperglycemia. Catalpol is a natural product isolated from the root of Rehmannia glutinosa, which has been reported to produce the effect of anti-diabetes in recent reports. The goal of the current study is to investigate the therapeutic effects of catalpol on hepatic insu...

The purpose of this article was to study the pharmacokinetic characteristics of YZG-331, plasma protein binding and metabolic stability in vivo and in vitro. Plasma and tissue concentrations of YZG-331 were determined in mice and rats after administration by LC-MS/MS analysis orally or intravenously. The plasma protein binding of YZG-331 with human...

Oxidative stress and autophagy dysfunction are critical factors in the pathogenesis of atherosclerosis. Adenosine 5′ monophosphate-activated protein kinase (AMPK) plays an important role in inhibiting oxidative stress and promoting autophagy. Catalpol, an iridoid glucoside extracted from the root of Rehmanniae glutinosa L, was reported to produce a...

Background Afatinib is an irreversible multi-targeted TKI, used in the treatment with EGFR mutated non-small cell lung cancer (NSCLC). The purpose of this study is to explore the molecular pharmacokinetic mechanism underlying the effect of P-gp inhibitors on the intestinal absorption and biliary excretion and to understand how P-gp inhibitors affec...

The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas. Here we report the identification of several classes of pyrimidine derivatives as potent BTK and JAK3 dual inhibitors. Among these molecules, approximately two thirds displayed strong inhibitory capacity at less th...

Physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estim...

Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a novel therapeutic strategy against cholestasis. Herein, we used a novel computational strategy with two-dimensional virtual screening for FXR agonists. For the first time, we found that auraptene...

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on dynamic process of alkal...

YZG-331, a synthetic adenosine derivative, express the sedative and hypnotic effects via binding to the adenosine receptor. The current study was taken to investigate the metabolic pathway of YZG-331 as well as species-specific differences in vitro. YZG-331 was reduced by 14, 11, 6, 46, and 11% within 120 min incubation in human, monkey, dog, rat,...

Background and aim: Nonalcoholic fatty liver disease (NAFLD) has become a major health concern worldwide. The present study was designed to investigate the effects of calycosin against high fat diet (HFD)-induced NAFLD in mice. Methods: C57BL/6J male mice were fed with HFD to induce NAFLD model and treated with or without calycosin for 12 weeks....

Recently, a new target Ca(2+) -binding protein SORCIN was reported to participate in multidrug resistance (MDR) in cancer. Here we aim to investigate whether dihydromyricetin (DMY), a dihydroflavonol compound with anti-inflamatory, anti-oxidant, anti-bacterial and anti-tumor actions, reverses MDR in MCF-7/ADR and K562/ADR and to elucidate its poten...

Recently, accumulating evidence has indicated that glucocorticoid-induced osteoporosis (GIOP) is closely related to oxidative stress and apoptosis. Alpha-lipoic acid (LA), a naturally endogenous anti-oxidant, possesses anti-oxidative and anti-apoptosis activities, implicating LA as a therapeutic agent for the treatment of GIOP. In this study, the o...

Cefditoren, a β-lactam antibiotic, is widely used in respiratory tract and skin infections in the clinic. This study was aimed at investigating the mechanism underlying hepatic uptake of cefditoren in rats and humans. Cmax of cefditoren plasma exposure was increased (0.80 ± 0.06 to 1.02 ± 0.16 μg mL⁻¹) when co-administrated with rifampicin. Extract...

We investigated the reversal effect of afatinib (AFT) on activity of adriamycin (ADR) in A549T cells and clarified the related molecular mechanisms. A549T cells overexpressing P-glycoprotein (P-gp) were resistant to anticancer drug ADR. AFT significantly increased the antitumor activity of ADR in A549T cells. AFT increased the intracellular concent...

Rhein is identified as a major metabolite of diacerein, a prodrug used in the treatment of osteoarthritis. Methotrexate (MTX) is a highly toxic drug with a low therapeutic index. MTX and diacerein are used concomitantly in clinical practice for the treatment of rheumatoid arthritis. The purpose of this study was to investigate organic anion transpo...

Cilostazol undergoes extensive liver metabolism. However, the transporter-mediated hepatic disposition of cilostazol remains unknown. The present study was performed to investigate the hepatic uptake and biliary excretion of cilostazol and its metabolites (OPC-13015 and OPC-13213) using rat liver and human transporter-transfected cells in vitro. Ci...

Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection....

Nephrotoxicity is one of major side effects of cisplatin in chemotherapy. Therefore, there is an urgent medical need to develop drugs that may protect kidney from toxicity. In previous study, we found that it showed the protective effects of formononetin against apoptosis by upregulating Nrf2. In this study, we investigated the renoprotective effec...

Multidrug resistance (MDR) leads to poor efficiency of chemotherapy. Overexpression of membrane transporters including P-gp could result in MDR. In this study, we investigated the effect of the combination of dasatinib (DA) and menadione (MQ) on P-gp-mediated MDR in the human leukemia K562/Adr cell line. The combination of DA and MQ had a stronger...

Catalpol is a natural product isolated from the root of Rehmannia glutinosa, and contributes to multiple pharmacological functions. Here, we showed the protective effects of catalpol against the alteration of cholesterol homeostasis in non-alcoholic fatty liver disease (NAFLD), and further investigated the role of endoplasmic reticulum stress (ER s...

Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/...

Background: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. Purpose: The present study was to investigate the hepatoprotective effe...

Acute kidney injury (AKI) is a well-known organ injury frequently observed after rhabdomyolysis (RM). The purposes of this study are to investigate the protective effects of formononetin on RM-mediated AKI and to elucidate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) in preventing apoptosis in vivo and in vitro. A rat model...

A new series of diphenylpyrimidine derivatives (DPPYs) bearing various aniline side chains at the C-2 position of pyrimidine core were synthesized as potent BTK inhibitors. Most of these inhibitors displayed improved activity against B leukemia cell lines compared with lead compound spebrutinib. Subsequent studies showed that the peculiar inhibitor...

Aim: Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in...

Non-alcoholic steatohepatitis (NASH) is a syndrome with simultaneous severe hepatic steatosis, lobular inflammation and pericelluar fibrosis. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside from edible botanical glycyrrhiza glabra, on NASH induced by a methionine and...