A review of the pharmacological effects of Arctium lappa (burdock)

Abstract Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock

Anti-inflammatory effect of gallic acid on HaCaT keratinocytes through the inhibition of MAPK-, NF-kB-, and Akt-dependent signaling pathways

The objectives of the present study were to evaluate the antioxidant and anti-inflammatory effects of gallic acid, a naturally occurring triphenolic compound, on HaCaT keratinocytes and study its mechanisms of action. The results showed that gallic acid at concentrations lower than 30 µM was non-toxic to HaCaT cells, reduced the intracellular level of reactive oxygen species, and suppressed the release of chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor-α- and interferon-γ-stimulated HaCaT keratinocytes. In addition, gallic acid reduced the total protein expression of NF-κB and inhibited the phosphorylation of ERK1/2, p38 MAPK, and Akt in stimulated HaCaT keratinocytes. In conclusion, our study revealed that gallic acid exhibited antioxidant and anti-inflammatory effects on keratinocytes, probably through the inhibition of MAPK-, NF-κB-, and Akt-dependent signaling pathways

Protective Effect of <i>Aquilaria crassna</i> Leaf Extract against Benzo[a]pyrene-Induced Toxicity in Neuronal Cells and <i>Caenorhabditis elegans</i>: Possible Active Constituent Includes Clionasterol

Aquilaria crassna (AC) is a beneficial plant widely used to alleviate various health ailments. Nevertheless, the neuroprotection, antiaging, and xenobiotic detoxification against high benzo[a]pyrene induction have not been investigated. This study aimed to investigate the effects of ethanolic extract of AC leaves (ACEE) in vitro using SH-SY5Y cells and in vivo using Caenorhabditis elegans (C. elegans). Neuroprotective activities and cell cycle progression were studied using SH-SY5Y cells. Additionally, C. elegans was used to determine longevity, health span, and transcriptional analysis. Furthermore, ACEE possible active compounds were analyzed by gas chromatograph–mass spectrometry (GC-MS) analysis and the possible active compounds were evaluated using a molecular docking study. First, ACEE possessed neuroprotective effects by normalizing cell cycle progression via the regulation of AhR/CYP1A1/cyclin D1 pathway. Next, ACEE played a role in xenobiotic detoxification in high B[a]P-induced C. elegans by the amelioration of lifespan reduction, and body length and size decrease through the reduction in gene expression in hexokinase (hxk) and CYP35 pathway. Finally, phytochemicals of ACEE were identified and we uncovered that clionasterol was the possible active constituent in powerfully inhibiting both CYP1A1 and hexokinase II receptor. Essentially, ACEE was recognized as a potential alternative medicine to defend against high B[a]P effects on neurotoxicity and xenobiotic detoxification

Potentiation of EDHF-mediated relaxation by chloride channel blockers

Aim: To investigate the involvement of Cl− channels in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in rat mesenteric arteries. Methods: Cl− channel and Kir channel activities were studied using whole-cell patch clamping in rat mesenteric arterial smooth muscle cells. Isometric tension of arterial rings was measured in organ chambers. Results: The volume-activated Cl− current in rat mesenteric arterial smooth muscle cells was abolished by Cl− channel blockers NPPB or DIDS. The EDHF-mediated vasorelaxation was potentiated by NPPB and DIDS. The EDHF response was diminished by a combination of apamin and charybdotoxin, which agreed with the hypothesis that EDHF response involves the release of K+ via the Ca2+-activated K+ channels in endothelial cells. The elevation of K+ concentration in bathing solution from 1.2 mmol/L to 11.2 mmol/L induced an arterial relaxation, which was abolished by the combination of BaCl2 and ouabain. It is consistent to the hypothesis that K+ activates K+/Na+-ATPase and inward rectifier K+ (Kir) channels, leading to the hyperpolarization and relaxation of vascular smooth muscle. The K+-induced relaxation was augmented by NPPB, DIDS, or withdrawal of Cl− from the bathing solution, which could be reversed by BaCl2, but not ouabain. The potentiating effect of Cl− channel blockers on K+-induced relaxation was probably due to the interaction between Cl− channels and Kir channels. Moreover, the K+-induced relaxation was potentiated when the arteries were incubated in hyperosmotic solution, which is known to inhibit volume-activated Cl− channels. Conclusion: The inhibition of Cl− channels, particularly the volume-activated Cl− channels, may potentiate the EDHF-induced vasorelaxation through the Kir channels

Extract of scutellaria baicalensis Georgi root exerts protection against myocardial ischemia-reperfusion injury in rats

Ischemic heart disease is a major cause of death in the world. Common therapies, such as primary coronary angioplasty and thrombolysis, are applied to restore blood supply to the heart, limit infarct size and reduce mortality. However, the restoration of blood supply would generate reactive oxygen species in damaged sites of the myocardium, intensifying the damage to the cardiac tissues. Radix Scutellariae baicalensis (Huangqin) is a well-known herb in traditional Chinese medicine with high antioxidant power. In this study, extract of the dry root of Scutellaria baicalensis Georgi (Sb) was confirmed to have a high content of flavonoids and phenolic compounds. The cardioprotective effects of the Sb extracts (3, 30 and 300 mg/kg) were evaluated in myocardial ischemia-reperfusion injuried rats. The results showed that animals that had received five-day pretreatment of the Sb extract (30 mg/kg) had a significant reduction in myocardial infarct size and a marked increase in the activity of catalase in the liver. The Sb extract could additionally enhance acetylcholine-induced vasorelaxation. It was proposed that the Sb extract exerted its cardioprotection by stimulating the catalase activity and improving vascular elasticity

Relaxation effect of narirutin on rat mesenteric arteries via nitric oxide release and activation of voltage-gated potassium channels

Narirutin is one of the most common flavanones found in citrus fruits. The vascular effects of its analogues naringenin and naringin have been reported but its effects on the cardiovascular system are largely unknown. In this study, relaxation effect of narirutin and its mechanisms of action were investigated by measuring isometric tension in rat mesenteric arteries. Patch-clamping was also used to study the effect of narirutin on potassium channels in vascular smooth muscle cells. Moreover, its effects on phosphorylation of endothelial nitric oxide synthase, cAMP level and phosphodiesterase activity in rat mesenteric arteries were studied by Western blot and biochemical assays. The results showed that pre-incubation of rat mesenteric arteries with narirutin had no influence on acetylcholine-induced endothelial-dependent relaxation. However, narirutin caused a direct concentration-dependent relaxation in rat mesenteric arteries. This relaxation effect was comparable to that of narirutin's structural analogue naringenin. Narirutin-induced relaxation was reduced by the removal of endothelium, NG-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor), and 4-aminopyridine (a voltage-gated potassium channel blocker). In addition, narirutin increased the phosphorylation of endothelial nitric oxide synthase and increased the voltage-dependent potassium current in mesenteric arterial smooth muscle cells. These effects were abolished by protein kinase A inhibitor. Furthermore, narirutin could increase cAMP level and inhibit phosphodiesterase activity in rat mesenteric arteries. In conclusion, narirutin has vasorelaxing effect and the mechanism involves the inhibition of phosphodiesterase, which increases intracellular cAMP, thereby stimulating the endothelial nitric oxide synthase and activating the voltage-gated potassium channels in vascular smooth muscle cells

Anti-metastatic effects of AGS-30 on breast cancer through the inhibition of M2-like macrophage polarization

AGS-30, a new andrographolide derivative, showed significant anticancer and anti-angiogenic characteristics. However, its role in controlling macrophage polarization and tumor immune response is unknown. Thus, the main goals of this study are to investigate how AGS-30 regulates macrophage polarization and how it suppresses breast cancer metastasis. AGS-30 inhibited IL-4 and IL-13-induced RAW 264.7 and THP-1 macrophages into M2-like phenotype. However, AGS-30 did not affect the LPS and IFN-γ-induced polarization of M1-like macrophages. AGS-30 reduced the mRNA expressions of CD206, Arg-1, Fizz-1, Ym-1, VEGF, IL-10, MMP2, and MMP9 in M2-like macrophages in a concentration-dependent manner. In contrast, andrographolide treatment at 5 μM did not affect M1-like and M2-like macrophage polarization. The conditioned medium from M2-like macrophages increased 4T1 breast cancer cell migration and invasion, whereas AGS-30 inhibited these effects. In the 4T1 breast tumor xenograft mice, the tumor volume and weight were reduced without affecting body weight after receiving AGS-30. AGS-30 treatment also reduced lung and liver metastasis, with reduced STAT6, CD31, VEGF, and Ki67 protein expressions. Moreover, the tumors had considerably fewer M2-like macrophages and Arg-1 expression, but the proportion of M1-like macrophages and iNOS expression increased after AGS-30 treatment. Same results were found in the tail vein metastasis model. In conclusion, this study shows that AGS-30 inhibits breast cancer growth and metastasis, probably through inhibiting M2-like macrophage polarization. Our findings suggest that AGS-30 may be a potential immunotherapeutic alternative for metastatic breast cancer

Relaxation effect of abacavir on rat basilar arteries

Background: The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods: The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results: Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion: Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction as abacavir does not impair relaxation of blood vessels. The most likely explanation of increased cardiovascular risk may be increased platelet aggregation as suggested by other studies

Serum nitric oxide synthase activity is a novel predictor of impaired vasorelaxation in rats

1. It is well documented that both acetylcholine (ACh)-evoked arterial relaxation and brachial artery flow-mediated vasodilatation are blunted in hypercholesterolaemic patients. However, there are no simple diagnostic methods to detect the pathology of blood vessels of patients. 2. To establish the use of serum nitric oxide synthase (NOS) activity as a diagnostic parameter for impaired vasorelaxation, animals with different levels of vascular healthiness were made by feeding Sprague–Dawley rats a normal diet, a high-cholesterol diet (HCD) or an HCD supplemented with 10 mg/kg per day, p.o., simvastatin, a cholesterol-lowering drug, for 30 days. Serum total cholesterol levels, serum NOS activity and ACh-induced vasorelaxation of the isolated aorta were determined at the end of the experiment. 3. Consumption of HCD for 30 days resulted in an increase in serum total cholesterol, attenuated ACh-induced nitric oxide/endothelium-dependent aortic relaxation and decreased NOS activity. Concomitant administration of simvastatin lowered the elevated blood cholesterol levels with complete reversal of the attenuated ACh-induced aortic relaxation and serum NOS activity. An attempt was made to correlate serum NOS activity and the magnitude of ACh-elicited vascular relaxation among the different groups. A positive correlation (r = 0.8329; P \u3c 0.001; n = 30) was found between serum NOS activity and vascular relaxation. 4. This finding is a good foundation for the development of a simple and low-cost alternative for diagnosing vascular diseases and evaluating the effectiveness of drugs on the vascular system in patients

Amauroderma rugosum Protects PC12 Cells against 6-OHDA-Induced Neurotoxicity through Antioxidant and Antiapoptotic Effects

Amauroderma rugosum (AR) is a dietary mushroom in the Ganodermataceae family whose pharmacological activity and medicinal value have rarely been reported. In this study, the antioxidant capacity and neuroprotective effects of AR were investigated. The aqueous extract of AR was confirmed to contain phenolic compounds, polysaccharides, and triterpenes. The results of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and total antioxidant capacity assays revealed that AR extract scavenged reactive oxygen species. Moreover, AR extract decreased the cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis of PC12 cells induced by 6-hydroxydopamine (6-OHDA). In addition, 6-OHDA upregulated the expressions of proapoptotic proteins and downregulated the Akt (protein kinase B)/mTOR- (mammalian target of rapamycin-) and MEK (mitogen-activated protein kinase kinase)/ERK- (extracellular signal-regulated kinases-) dependent signaling pathways. These effects of 6-OHDA were abolished or partially reversed by AR extract. Furthermore, the neuroprotective effects of AR in 6-OHDA-treated PC12 cells were significantly abolished by Akt and MEK inhibitor. Thus, AR extract possesses neuroprotective effects, probably through its antioxidant and antiapoptotic effects. These findings suggest the potential application of AR in the prevention or treatment of oxidative stress-related neurodegenerative diseases such as Parkinson’s disease