Kidney protective potential of lactoferrin: pharmacological insights and therapeutic advances

Md,Sarwar Zahan,Kazi Ahsan Ahmed,Akhi Moni,Alessandra Sinopoli,Hunjoo Ha,Md Jamal Uddin 대한생리학회-대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.1

Kidney disease is becoming a global public health issue. Acute kidney injury (AKI) and chronic kidney disease (CKD) have serious adverse health outcomes. However, there is no effective therapy to treat these diseases. Lactoferrin (LF), a multi-functional glycoprotein, is protective against various pathophysiological conditions in various disease models. LF shows protective effects against AKI and CKD. LF reduces markers related to inflammation, oxidative stress, apoptosis, and kidney fibrosis, and induces autophagy and mitochondrial biogenesis in the kidney. Although there are no clinical trials of LF to treat kidney disease, several clinical trials and studies on LF-based drug development are ongoing. In this review, we discussed the possible kidney protective mechanisms of LF, as well as the pharmacological and therapeutic advances. The evidence suggests that LF may become a potent pharmacological agent to treat kidney diseases.

Carbon monoxide releasing molecule-2 protects mice against acute kidney injury through inhibition of ER stress

Md Jamal Uddin,Eun Seon Pak,Hunjoo Ha 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

Inhibitory Effects of <i>Chung Hun Wha Dam Tang</i> (CHWDT) on High-Fat Diet-Induced Obesity via AMP-Activated Protein Kinase Activation

Uddin, Md. Jamal,Joe, Yeonsoo,Zheng, Min,Kim, Sena,Lee, Hoyoung,Kwon, Tae-Oh,Chung, Hun Taeg Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P>The <I>Chung Hun Wha Dam Tang</I> (CHWDT) herbal combination was reported to cease dizziness and phlegm. However, the effect of CHWDT in obesity has not yet been known mechanically. Therefore, we investigated whether this CHWDT could protect the cells from lipogenesis, gluconeogenesis, and inflammation in both in vivo and in vitro. CHWDT significantly decreased body weight, epididymal and perirenal fat content without affecting feed intake in high-fat diet-induced obese mice model. Additionally, CHWDT inhibited obesity-induced SREBP1, FAS, PGC1<I><I>α</I></I>, G6Pase, PEPCK and increased CPT1, ACO, and LCAD genes expression in vivo and in vitro. Proinflammatory cytokines like TNF-<I><I>α</I></I> and iNOS expression were reduced by CHWDT in both Raw264.7 macrophages and HepG2 cells. In addition, NO production was also significantly decreased by CHWDT in LPS-stimulated macrophages. Furthermore, AMPK<I><I>α</I></I> activation by CHWDT was involved in inhibition of obesity by reducing triglycerides production and increasing CPT1 expression. Based on all of the results, we suggest that CHWDT has inhibitory effects on obesity-induced lipogenesis, gluconeogenesis, and inflammation via AMPK<I><I>α</I></I> activation.</P>

Carbon Monoxide Attenuates Dextran Sulfate Sodium-Induced Colitis via Inhibition of GSK-3 <i><i>β</i></i> Signaling

Uddin, Md. Jamal,Jeong, Sun-oh,Zheng, Min,Chen, Yingqing,Cho, Gyeong Jae,Chung, Hun Taeg,Joe, Yeonsoo Hindawi Publishing Corporation 2013 Oxidative medicine and cellular longevity Vol.2013 No.-

<P>Endogenous carbon monoxide (CO) is produced by heme oxygenase-1 (HO)-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3<I><I>β</I></I> in mice model. To support the in vivo observation, TNF-<I><I>α</I></I>, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs) and bone marrow-derived macrophages (BMMs) from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3<I><I>β</I></I> activation and decreased TNF-<I><I>α</I></I> and iNOS expression by inhibition of NF-<I><I>κ</I></I>B activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3<I><I>β</I></I> signaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3<I><I>β</I></I> in DSS-induced colitis model.</P>

Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury

( Md Jamal Uddin ),( Debra Dorotea ),( Eun Seon Pak ),( Hunjoo Ha ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.3

Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a nonreceptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.

A functional link between heme oxygenase-1 and tristetraprolin in the anti-inflammatory effects of nicotine

Jamal Uddin, Md.,Joe, Yeonsoo,Zheng, Min,Blackshear, Perry J.,Ryter, Stefan W.,Park, Jeong Woo,Chung, Hun Taeg Elsevier 2013 FREE RADICAL BIOLOGY AND MEDICINE Vol.65 No.-

<P><B>Abstract</B></P> <P>Nicotine stimulates the cholinergic anti-inflammatory pathway and prevents excessive inflammation by inhibiting the release of inflammatory cytokines from macrophages. We have previously reported that heme oxygenase-1 (HO-1) and tristetraprolin (TTP) are induced by nicotine and mediate the anti-inflammatory function of nicotine in macrophages. However, it was not clear whether the two molecules are functionally linked. In this study, we sought to determine whether HO-1 associates with TTP to mediate the anti-inflammatory effects of nicotine. Inhibition of HO-1 activity or HO-1 expression attenuated the effects of nicotine on STAT3 activation, TTP induction, and TNF-α production in LPS-treated macrophages. Induction of HO-1 expression increased the level of TTP in the absence of nicotine. In an LPS-induced endotoxemia model, HO-1 deficiency blocked the effects of nicotine on the STAT3 phosphorylation, TTP induction, and LPS-induced TNF-α production in the liver. Downregulation of STAT3 by siRNA attenuated the effect of nicotine on TTP expression and TNF-α production but did not affect the nicotine-mediated induction of HO-1. In TTP knockout mice, nicotine treatment enhanced HO-1 expression and STAT3 activation but failed to inhibit LPS-induced TNF-α production. Our results suggest that HO-1 and TTP are functionally linked in mediating the anti-inflammatory effects of nicotine; HO-1 is necessary for the induction of TTP by nicotine. This novel nicotine–HO-1–TTP signaling pathway provides new possibilities for the treatment of inflammatory diseases.</P>

Carbon monoxide releasing molecule-2 protects mice against acute kidney injury through inhibition of ER stress

Uddin, Md Jamal,Pak, Eun Seon,Ha, Hunjoo The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

Analgesic activity of the ethanolic extract of Aphanamixis polystachya bark

Md Faizul Hasan,,Razina Rouf,,Juwel Barua,,Shaikh Jamal Uddin,Jamil Ahmad Shilpi 경희대학교 융합한의과학연구소 2007 Oriental Pharmacy and Experimental Medicine Vol.7 No.4

Ethanolic extract of Aphanamixis polystachya bark was used to investigate its analgesic activity by acetic acid induced writhing in mice. The bark extract exhibited statistically significant and dose dependent analgesic activity in mice. The bark extract at the doses of 250 and 500 mg/kg body weight showed 40.69% and 62.07% writhing inhibition respectively in mice whereas diclofenac- Na produced 75.17% writhing inhibition as a positive control.

Chemical characterization and bioactivity of Trichosanthes dioica edible shoot extract

Md. Nazmul Hasan Zilani,Shaikh Jamal Uddin,Hemayet Hossain,Hazrina Hazni,Jamil A. Shilpi,Md. Golam Hossain 경희대학교 융합한의과학연구소 2018 Oriental Pharmacy and Experimental Medicine Vol.18 No.2

Present investigation was aimed to evaluate the traditional use of edible part of soft shoots of Trichosanthes dioica Roxb. (Cucurbitaceae) as an antidiabetic in mice model. In addition, antioxidant activity and chemical profiling of this plant part were also performed to support its observed activity. The extract was subjected to oral glucose tolerance test in normal and alloxan induced diabetic mice to explore its antihyperglycemic activity. Antioxidant capacity was analyzed by a number of in vitro assays. Quantification of bioactive polyphenols was done by HPLC. Liquid Chromatography coupled with Mass Spectrometry (LCMS) was used to identify chemical constituents present in the extract. Total polyphenol and flavonoids content were found in significant quantity. In DPPH radical scavenging assay the IC50 value of the extract was found to be 148.62 µg/mL. Reducing power of the extract was comparable with that of butylatedhydroxytoluene (BHT). HPLC analysis indicated that quercetin, rutin, p-coumaric acid and kaempferol were the major bioactive polyphenols present in the extract. Further chemical profiling using LCMS analysis was identified a total of nine compounds with different chemical classes. In OGTT, extract (400 mg/kg BW) showed a 31.13% decrease (p < 0.05) in blood glucose levels at 30 min compared to the normal control. In alloxan induced diabetic mice the extract at the doses of 200 mg and 400 mg/kg, showed significant decrease (p < 0.05) of blood glucose level compared to diabetic control. The extract showed oral glucose tolerance potential and antioxidant capacity which might be due to the presence of different compounds such as quercetin, rutin, kaempferol, oleanolic acid, β-sitosterol. The results support the scientific basis of it ethnobotanical uses in traditional medicinal practices of Bangladesh.

Cytotoxicity and antinociceptive activity of Jasminum sambac leaves

Md Rahatul Islam,Razina Rouf,Juwel Barua,Shaikh Jamal Uddin,Mahiuddin Alamgir 경희대학교 융합한의과학연구소 2008 Oriental Pharmacy and Experimental Medicine Vol.8 No.2

The ethanolic extract of Jasminum sambac leaves were tested for its cytotoxicity and possible antinociceptive activity in experimental animals. The extract showed potent cytotoxic activity in brine shrimp lethality assay and the LC50 was found only 25 mg/ml. The extract significantly and dose dependently inhibited the acetic acid induced writhing in mice (56.83%, P < 0.001 and 43.17%, P < 0.001 for 500 and 250 mg/kg body weight, respectively). The results supported its traditional uses. The ethanolic extract of Jasminum sambac leaves were tested for its cytotoxicity and possible antinociceptive activity in experimental animals. The extract showed potent cytotoxic activity in brine shrimp lethality assay and the LC50 was found only 25 mg/ml. The extract significantly and dose dependently inhibited the acetic acid induced writhing in mice (56.83%, P < 0.001 and 43.17%, P < 0.001 for 500 and 250 mg/kg body weight, respectively). The results supported its traditional uses.