Hepato- and reno-protective effects of thymoquinone, crocin, and carvacrol: A comprehensive review

Medicinal plants are rich in nutrients and phytochemicals which prevent and treat a wide range of ailments. Accumulating experimental studies exhibit that some bioactive ingredients extracted from medicinal plants have suitable therapeutic effects on hepatic and renal injuries. This review focuses on the hepato- and reno-protective effects of thymoquinone, crocin, and carvacrol. The relevant literature was retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases from the beginning of 2015 until the end of November 2021. According to the scientific evidence, the considered phytochemicals in this review have been applied with useful therapeutic effects on hepatic and renal damage. These therapeutic effects were mainly mediated through the amelioration of oxidative stress, suppression of inflammatory responses, and inhibition of apoptosis. Intracellular signaling pathways linked to nuclear factor kappa B (NF-κB), adenosine monophosphate-activated protein kinase, c-jun N-terminal kinase, and extracellular signal-regulated kinase 1/2 and Toll-like receptors are the most important pathways targeted by these phytochemicals. Up-regulation of transcription factor Nrf2 and down-regulation of transforming growth factor-beta 1 by these natural compounds also contribute to the alleviation of hepatic and renal injuries.

Lesão renal aguda induzida pela sepse e potenciais terapias renoprotetoras / Acute kidney injury induced by sepsis and potential renoprotective therapies

A lesão renal aguda (LRA) é uma complicação comum no paciente grave e está associada à alta mortalidade, tendo a sepse como o mais prevalente fator de risco em pacientes críticos. A LRA na sepse está envolvida com estresse oxidativo e vasoconstrição. Diversas medidas terapêuticas para minimizar os danos renais na sepse já foram investigadas, com destaque para os fármacos antioxodantes, e não se confirmaram como intervenção a ser incorporada na clínica. O objetivo desse estudo foi avaliar a resposta inflamatória sistêmica na sepse, a função renal e os efeitos renoprotetores do vasodilatador cilostazol e dos antioxidantes n-acetilcisteína (NAC) e diosmina hesperidina no modelo de sepse experimental. Foram avaliados parâmetros sistêmicos, o perfil inflamatório renal, intestinal e pulmonar (TGF- e interleucina 6-IL-6), a função renal (FR-clearance de creatinina), a geração urinária de peróxidos (PU) e a análise histopatológica dos rins. Foram utilizados ratos Wistar, machos, divididos em 5 grupos: Sham (controle); Sepse: sepse induzida pela técnica de ligadura e punção do cecon (LPC); Sepse+Cilostazol; Sepse+N-acetilcisteína (NAC) e Sepse+Diosmina. Os resultados mostraram que o grupo Sepse apresentou elevação de TGF- e IL-6 e parâmetros globais como redução da temperatura e hipotensão que caracterizaram o padrão da sepse. Os grupos sepse, tratados ou não, mostraram redução da função renal, com diminuição do fluxo urinário e elevação do parâmetro oxidante analisado, os PUs. Apenas o grupo Sepse+Diosmina demonstrou atenuar a redução da FR desencadeada pela sepse e redução dos PUs na comparação ao grupo Sepse. Todos os grupos sepse apresentaram alterações histológicas renais. O estudo confirmou a LRA por sepse, sendo que apenas o fármaco diosmina hesperidina contribuiu para a melhora da função renal e redução do estresse oxidativo.

Acute renal injury (AKI) is a common complication in critically ill patient and it is associated with high mortality, with sepsis being the most prevalent risk factor for renal failure in critically ill patients. LRA in sepsis is involved with oxidative stress and vasoconstriction. Therapeutic initiatives aimed at minimizing renal damage in sepsis were not confirmed. This study evaluated the systemic inflammatory response in sepsis, renal function and renoprotective effects of the vasodilator cilostazol and the antioxidants n-acetylcysteine (NAC) and diospenes hesperidin. Systemic parameters, the inflammatory renal, in the intestine and in the lungs profile (TGF- and interleukin 6-IL-6), renal function (RF-creatinine clearance), urinary peroxides generation (PU) and histopathological analysis of the kidneys were performed. Male Wistar rats were divided into 5 groups: Sham (control); Sepsis: sepsis induced by the technique of ligation and puncture of the cecon (LPC); Sepsis+cilostazol; Sepsis+N-acetylcysteine (NAC) and Sepsis+diosmin. The results showed that the Sepsis group presented elevation of TGF- and IL-6 and global parameters such as temperature reduction and hypotension characterizing the sepsis pattern. Sepsis groups showed reduced renal function and urinary flow and elevation on UPs. The Sepsis+Diosmina group was the only one to attenuate RF reduction and PU reduction when compared to the Sepsis group. All sepsis groups had renal histological changes. The study confirmed that sepsis induces AKI, being diosmin hesperidin the only agent to contribute to the improvement of renal function and reduction of oxidative stress.

Efecto reno-protector y reno-reparador del Factor de Crecimiento Epidérmico en biomodelo de Insuficiencia Renal Crónica / Reno-protective and reno-restorative effect of the Epidermal Growth Factor in biomodel of Chronic Renal Failure

Introducción: La Enfermedad Renal es un problema de salud mundial. El Factor de Crecimiento Epidérmico actúa como citoprotector y trófico reparador. Objetivo: Evaluar el efecto reno-protector y reno-reparador del Factor de Crecimiento Epidérmico en biomodelo de Insuficiencia Renal Crónica. Material y Métodos: Se estudiaron 120 ratas, Wistar, en 6 grupos: Control Negativo y positivo, Solución Salina Dosis Única y Múltiple, Factor de Crecimiento Epidérmico Dosis Única y Múltiple. Se aplicó para efecto reno-protector dosis única antes del daño, y para el reno-reparador dosis múltiples posterior al daño, a razón de 100 µg/kg de peso. Resultados: La creatinina, urea y ácido úrico disminuyeron significativamente en los grupos experimentales, con mayor disminución para el grupo experimental dosis única, por lo que el efecto reno-protector fue mayor que el reno-reparador para los esquemas de tratamiento utilizados. Conclusiones: El Factor de Crecimiento Epidérmico mostró efecto reno-protector y reno-reparador al disminuir las variables hematológicas de daño renal(AU)

Introduction: Kidney disease is a world health problem. Epidermic Growth Factor acts as cyto-protector, and trophic restorative. Objective: To assess the reno-protective and reno-restorative effect of the Epidermal Growth Factor in biomodel of Chronic Renal Failure. Material and Methods: 120 Wistar rats were studied in 6 groups: Negative and Positive Control, Saline Solution Single-Dose and Multiple-Dose, Epidermal Growth Factor Single-Dose and Multiple-Dose. A single dose was applied before the damage for the reno-protective effect, and multiple doses after the damage for the reno-restorative effect, at a rate of 100 µg/kg of weight. Results: Creatinine, urea, and uric acid diminished significantly in the experimental groups, with a higher decrease for experimental group with single dose; therefore, the reno-protective effect was higher than reno-restorative one for the treatment patterns used. Conclusions: Epidermal Growth Factor showed reno-protective and reno-restorative effect by diminishing the hematological variables in kidney damage(AU)

Impact of Chrysanthemum fontanesii extract on sodium valproate mediated oxidative damage in mice kidney.

The objective of this study was to evaluate the potential of n-butanol extract obtained from flowers of Chrysanthemum fontanesii (Cf) and vitamin E against kidney oxidant injury induced by sodium valproate in mice. The evaluation was made through Histopathological examination and measuring kidney lipid peroxidation (LPO) and antioxidant parameters: reduced glutathione (GSH), glutathione peroxidase (GPx) and catalase. Severe alterations in all biomarkers were observed after injury with VPA. Treatment with Cf extract and vitamin E resulted in markedly decreased levels of LPO while increased levels of GSH and antioxidant enzymes activities were observed. In conclusion, n-butanol extract of Cf may be an interesting candidate for the treatment of kidney injury induced by VPA through enhancing endogenous antioxidant defenses and normalizing the kidney histopathological architecture.

Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices.

Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub-chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman’s capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman’s space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination.

Effect of berberine on the expression of nephrin, podocin and intergrin α3β1 in diabetic nephropathy rats / 中国药理学通报

Aim To investigate the effect of berberine on the expression of nephrin, podocin and intergrinα3β1 in diabetic nephropathy ( DN ) rat model, and further probe in to the renoprotective effects of berber-ine and its potential mechanisms. Methods The rat model of DN was induced by intraperitoneal injection of streptozotocin ( STZ ) after fed with high-sugar and high-fat diet for six weeks. The rats were assigned into 6 groups randomly: normal control group, DN model group, BBR (50,100 and 200 mg·kg-1 ) treatment group and enalaprilat positive control group ( 1 mg · kg-1 ) . The distribution and expression of kidney podocyte related proteins nephrin, podocin and interg-rinα3β1 were detected by immunohistochemical meth-od following electron microscopy observation ( × 1000 ) and high magnification observation( × 400) and West-ern blot. Results The podocyte related protein neph-rin, podocin and intergrin α3β1 were mainly distribu-ted in podocyte, but slightly different. Compared with normal control group, the expresion of podocyte related protein nephrin, podocin and intergrin α3β1 was de-creased obviously; compared with model group, BBR (100 and 200 mg·kg-1 ) treatment group could sig-nificantly suppress the abnormalities of pathological changes of the kidney and upregulate the expression levels of podocyte specific protein nephrin, podocin and intergrin α3β1 in the kidney of diabetic rats with nephropathy. Conclusions Berberine could alleviate the abnormalities of kidney pathological changes and proteinuria production in the DN model rats, which may be related to the upregulation of the expression of the podocyte proteins nephrin, podocin and intergrinα3β1.

Effect of berberine on expression of vascular endothelial growth factor in diabetic nephropathy rats / 中国药理学通报

Aim To investigate the renoprotective effect of berberine in diabetic nephropathy rat model. Methods The rat model of DN was induced by intra-peritoneal injection of streptozotocin ( STZ ) after fed with high sugar and high fat diet for six weeks. The rats were divided into 5 groups randomly, i. e. normal control group, model group, BBR ( 50 mg · kg-1 ) , BBR ( 100 mg · kg-1 ) and BBR ( 200 mg · kg-1 ) treatment group. The fasting blood glucose ( FBG) was evaluated at 2, 4, 6,8 week respectively. The patho-logical changes in the kidney were determined by PAS staining. The expression of vascular endothelial growth factor ( VEGF) was detected by immunohistochemistry and Western blot respectively. Results Compared with normal control group, the value of FBG, SCr, BUN and UTP of model group were sharply increased. Compared with model group, the value of FBG in ber-berine different dosage treatment groups were signifi-cantly decreased to various degrees, and berberine dif-ferent dosage treatment could decrease the levels of SCr, BUN and UTP in different degree. Berberine could surpress the alterations of pathological changes in the kidneys and downregulate the expression levels of VEGF in the kidney of diabetic rats with nephropathy. Conclusion Berberine could significantly ameliorate the biochemical indicators and renal injury of the model rats through affecting the abnormal expression levels of VEGF in the kidney.

High-risk Hypertension and Its Clinical Implications.

Hypertension (HT) is a well-established risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). Only <50% of treated hypertensive patients have a BP of <140/90 mmHg, which is a cause for much concern. These treated but inadequately controlled hypertensive patients are at significant risk for developing CVD and other complications. Telmisartan is a long-acting angiotensin receptor blocker (ARB), which has multiple positive effects aside from its antihypertensive efficacy. It reduces CV events in high-risk patients, has favorable effects on endothelial function including renoprotective effects. Trials like the MAPHY and BCAP have shown that β blockers (metoprolol) have beneficial effects on outcomes and survival along with reduction in BP. Most hypertensives need combination approach to control their high BP. Being cardioprotective drugs, combination of telmisartan and metoprolol is beneficial for secondary prevention of cardiovascular events in high-risk patients with HT.

The effective dosage of angiotensin converting enzyme inhibitors (ACEI) in renoprotective effect / 中国实用内科杂志

Objective To investigate effective dosage of ACEI in renoprotective effect in primary glomerular dieases.Method In 154 patients with primary glomerular diseases,we performed a 4 month therapy,including 40 cases with high or low doses of captopril and 51 cases with high or low doses of cilazapril and 45 cases with high low doses of enalapril,and 18 cases with amlodipine as control.Mean arterial pressure (MAP),uninary protein,urinary albumin excretion rate and renal function were measured at basis and after 1,2,3,4 month of therapy,and ACE gene polymorphism was determined in these patients.Result 1.There were no difference on ACE gene polymorphism and diet protein and diet salt among control group and different ACEIs group;2.The antiproteinuria and the effect on renal function were same between patients with high and low dose of different ACEIs.Conclusion The low dose of ACEI has the same renoprotective effect as general dose in primary glomerular diseases.