HP Extract Research Articles

Permeability of Hypogymnia physodes Extract Component-Physodic Acid through the Blood-Brain Barrier as an Important Argument for Its Anticancer and Neuroprotective Activity within the Central Nervous System.

Simple SummaryCentral nervous system (CNS) diseases, including tumors such as glioblastomas and neurodegenerative diseases, such as Alzheimer’s disease, are some of the greatest challenges of modern medicine. Therefore, our study aimed to evaluate the anticancer and neuroprotective activity of the extract from a common European lichen Hypogymnia physodes and of its compound-physodic acid. The examined substances were cytotoxic against the glioblastoma cell lines A-172, T98G, and U-138 MG. Both substances strongly inhibited hyaluronidase, and diminished cyclooxygenase-2 activity (H. physodes extract), enzymes expressed in patients with malignant glioma. Furthermore, H. physodes extract inhibited tyrosinase activity, the enzyme linked to neurodegenerative diseases. The tested substances exhibited antioxidant activity, however, acetylcholinesterase and butyrylcholinesterase inhibitory activity were not high. We proved that physodic acid can cross the blood–brain barrier. We conclude that physodic acid and H. physodes extract should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially concerning CNS. Lichen secondary metabolites are characterized by huge pharmacological potential. Our research focused on assessing the anticancer and neuroprotective activity of Hypogymnia physodes acetone extract (HP extract) and physodic acid, its major component. The antitumor properties were evaluated by cytotoxicity analysis using A-172, T98G, and U-138 MG glioblastoma cell lines and by hyaluronidase and cyclooxygenase-2 (COX-2) inhibition. The neuroprotective potential was examined using COX-2, tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activity tests. Moreover, the antioxidant potential of the tested substances was examined, and the chemical composition of the extract was analyzed. For physodic acid, the permeability through the blood–brain barrier using Parallel Artificial Membrane Permeability Assay for the Blood–Brain Barrier assay (PAMPA-BBB) was assessed. Our study shows that the tested substances strongly inhibited glioblastoma cell proliferation and hyaluronidase activity. Besides, HP extract diminished COX-2 and tyrosinase activity. However, the AChE and BChE inhibitory activity of HP extract and physodic acid were mild. The examined substances exhibited strong antioxidant activity. Importantly, we proved that physodic acid crosses the blood–brain barrier. We conclude that physodic acid and H. physodes should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially regarding the central nervous system diseases.

Improvements in estrogen deficiency-induced hypercholesterolemia by Hypericum perforatum L. extract are associated with gut microbiota and related metabolites in ovariectomized (OVX) rats

Hypericum perforatum L. (HP), a well-known natural medicine, has a potential effect on menopausal hypercholesterolemia. However, the effect of HP extract on gut microbiota and related metabolites, which play vital roles in metabolic disease occurrence, in the context of estrogen deficiency have not yet been reported. The aims of the present study were to investigate the effects of HP extract on gut microbial composition and related metabolite profiles in ovariectomized (OVX) rats and reveal the relationships between pathological indicators and alterations in both gut microbial composition at the genus level and metabolites. Body weight, serum parameters, liver lipids and histomorphology were determined. Microbial composition was analyzed using 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and serum bile acids were quantitatively measured. Correlations between pathological indicators and alteration in gut microbiota and metabolites were investigated using Spearman's rank correlation test. Gene expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and cholesterol 27-hydroxylase (CYP27A1) in the liver and G protein-coupled receptors (GPCRs; GPR43 and GPR41), ZO-1 and occludin in the cecum were determined by PCR. Microbial composition and metabolite profiles were significantly changed in OVX rats compared with sham rats. Twelve bacterial genera, 5 SCFAs and 12 bile acids were identified as differential biomarkers. Differential genera, SCFAs and bile acids were closely associated with weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In OVX rats, HP administration can significantly reverse the pathological symptoms of body weight gain, serum lipid disorders and hepatic steatosis, at the meanwhile, reestablish gut microbial composition and metabolite profiles. Moreover, HP administration significantly upregulated the levels of CYP7A1, GPR43 and GPR41. In conclusion, HP can ameliorate estrogen deficiency-induced hypercholesterolemia. The underlying mechanism may be associated with improvements in gut microbiota composition and the profile of related metabolites as well as increases in bile acid secretion.

Haplophyllum Buxbaumii Ekstresinin Prostat Kanseri Üzerindeki Apoptotik Etkisi

Prostate cancer is a common type of cancer among men. Recently, studies on new anticancer agents of herbal origin in the treatment of cancer have increased. Haplophyllum buxbaumii (HP) is a perennial herbaceous plant. Studies have reported that Haplophyllum subspecies has antioxidant properties. And the anticancer effect of HP is unknown. This study aims to reveal the apoptotic effect HP on prostate cancer. The cytotoxic effect of HP was evaluated by the MTT method. In addition, apoptotic pathway mediators were analyzed by ELISA method. HP extract application reduced the viability of prostate cancer and activated the apoptotic mediators while decreasing anti-apoptotic mediators. Our study showed that HP extract has an antiproliferative and apoptotic effect on prostate cancer.

Antimicrobial, anticancer and antioxidant activities of nano-heart of Phoenix dactylifera tree extract loaded chitosan nanoparticles: In vitro and in vivo study

This study aimed to present a new heart of P. dactylifera (HP) extract loaded chitosan nanoparticles and estimate its anticancer, antimicrobial, antioxidant activity and free radical scavenger effect (in vitro). This nano-supplement may prevent doxorubicin cardiotoxicity and nephrotoxicity in rat model. The HP extract was loaded on chitosan nanoparticles producing HP–ChNPs, then characterized. The antioxidant properties of the HP–ChNPs was assessed in vitro. The antibacterial activity against three-gram positive bacteria and two gram-negative bacteria were done. The in vitro studies of cytotoxicity against MCF7, CaCo3, and Hela cell lines were also evaluated. Then, the protective effect of the HP–ChNPs (2 mg/kg, IP) was evaluated against doxorubicin induce organ toxicity in a rat model. The in vitro studies revealed the antibacterial, anticancer and antioxidant activities of the HP–ChNPs. The in vivo study demonstrates reduction of heart and kidney apoptosis with increased programmed cell death protein-1 (PD-1); as the major anticancer drug (doxorubicin) pathway is to release free radicals with decreased PD-1 levels and induction of apoptosis. In conclusion, the HP–ChNPs, in a very small dose, might be a promising supplement to avoid doxorubicin toxicity with improvment the antioxidant enzymes without affecting its anticancer activity.

Immune Modulating Qualities of Sorghum Polyphenols

Abstract Objectives The objective was to evaluate the potential anti-inflammatory effects of Sorghum polyphenolic extracts on raw 264.7 cells. Methods Sorghum polyphenols were extracted using a 70% ETOH and 5% citric acid solvent. Raw 264.7 cells were treated with either vehicle 1.25, or 0.625 mg/ml polyphenol extract from either a novel high polyphenol sorghum or SC84. Supernatant was harvested and Nitric Oxide was measured at a 12 hour time point. ELISA assay was performed to measure the concentrations of 12 anti-inflammatory associated cytokines. Cell morphology changes were observed at 3, 6, 12, and 24 hours using light microscopy. 84 genes associated with inflammation were measured via QPCR. Western blot analysis measured the expression of LC3 as well as STAT1, STAT3 and NF-kB nuclear translocation. Results Nitric Oxide was reduced by the sorghum extract (not significant). Cell morphology changed by developing vacuole like structures and an apparent decrease in cell number. ELISA analysis showed that Il-6 and Il-10 were significantly reduced in all treatments. SC84 extract showed an increase in G-CSF production in activated macrophages. QPCR revealed LPS and IFNY activated cells treated with HP extract showed an increase in the expression of 9 and decreased expression of 14 cytokine related genes compared to cells that had only been activated by LPS and IFN Y. When LPS and IFN Y activated cells were cotreated with SC84 extract, 15 cytokine related genes were upregulated and 16 cytokine related genes were downregulated. LC3 expression was measured via western blot and showed a dose dependent with 1.25 mg/ml showing statistical significance. STAT3 nuclear translocation induce by LPS/IFN Y was attenuated by sorghum polyphenols. Conclusions The sorghum polyphenols modulated immune response via a reduction in Th2 promoting cytokines IL-6 and IL-10. LC3 II expression increased with the concentration of the HP polyphenol extract treatment, suggesting autophagy. Funding Sources All funding was provided by the United States Department of Agriculture.

Investigation of Apoptotic Effects of Hypericum perforatum Extract on Breast Cancer Cell Line

Hypericum perforatum has biological active contents affecting a variety of proteins such as caspase-3, bcl-2, and bax, which mediate apoptosis known as programmed cell death and exerting anti-inflammatory effect. Apoptotic pathways are important for cancers, chemotherapeutic resistance, and cancer development. Anti-inflammatory agents are also a potential target for cancer. Therefore, it was aimed to investigate the activity of caspase-3 and the expressions of bcl-2, bax, wee 1, gadd153, grp78, AIF, iNOS, COX-2, cPLA2, and NF-κB in H. perforatum extract-treated breast cancer (BC) cells in this study. The activity of caspase-3 and the expressions of these proteins were determined in the cells by ELISA. The HP extract increased the activity of caspase-3 and the expressions of bax, wee 1, gadd153, grp78 and AIF, and decreased the expressions of bcl-2, COX-2, iNOS, cPLA2 and NF-κB in the BC cells. In the light of these findings, HP extract could help to inhibit grow of BC cells and its anti-inflammatory effect may contribute this effect.

Antiproliferative Effects of Free and Encapsulated Hypericum Perforatum L. Extract and Its Potential Interaction with Doxorubicin for Esophageal Squamous Cell Carcinoma.

ObjectivesEsophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30.MethodsNanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level.ResultsFree drugs and nanoparticles significantly inhibited KYSE30 cells by 55–73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04–0.06 mg/mL and ~ 0.6–0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05).ConclusionDox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

Commercial Lawsonia inermis L. dried leaves and processed powder: Phytochemical composition, antioxidant, antibacterial, and allelopathic activities

Henna (Lawsonia inermis L.) is a plant used over the world for centuries for its medical and cosmetic virtues. The present work aimed to determine the phytochemical composition, antioxidant, antibacterial activities and phytotoxic potentials of commonly commercialized henna’s dried leaves (HL) and processed powder (HP). The chromatographic method, using reversed-phase high-performance liquid chromatography, with diode array detection (RP-HPLC–DAD) coupled to electrospray ionization–mass spectrometry (ESI–MS), showed that HP and HL contained high polyphenolic content estimated to 31.35±2.05 and 20.22±0.23mg/g of dray starting material, respectively. Gallic acid (16.23%) and eugenol (13.74%) were the most abundant compounds, whereas, luteolin was the major compound in HL (43.41%). Additionally, HP extract showed the strongest antioxidant potentials as assessed by both DPPH and ABTS functional methods with IC50=51.36±1.9 and 78.18±1.47μg/ml, respectively. Antimicrobial potential evaluated using a range of microorganism strains demonstrated that Bacillus subtilis (ATCC6633) was the most sensitive bacteria to both HL and HP extracts with MBC≈165.8±3.7μg/ml (HP) and 454.3±42μg/ml (HL). The extracts allelopathic activity on seed germination, stem and root growth of wheat (Triticum aestivum L.) and canary grass (Phalaris canariensis L.) were also assessed in-vitro. Canary grass was the most sensitive species to HL and HP. Both extracts were effective inhibitors of germination, stem and root growth in a dose-dependent manner. These findings could support the potential applications of HL and HP extracts as natural herbicide. Obtained data reveal that commercial HP contained an additional product that strengthened its chemical and functional properties, particularly, clove (Syzygium aromaticum) which is frequently supplemented for henna’s cosmetic value improvement.

Comparative pharmacokinetics and brain distribution of magnolol and honokiol after oral administration of Magnolia officinalis cortex extract and its compatibility with other herbal medicines in Zhi-Zi-Hou-Po Decoction to rats.

Zhi-Zi-Hou-Po decoction (ZZHPD) is one of the famous antidepressant Chinese formulas and is composed of Magnolia officinalis cortex (HP), Gardenia jasminoides Ellis (ZZ) and Citrus aurantium L. (ZS). Magnolol (MN) and honokiol (HN) from HP are the major active ingredients responsible for the therapeutic effects of ZZHPD. The aim of this study is to compare the pharmacokinetics and rat brain distribution of MN and HN after oral administration of HP extract and its compatibility with other herbal medicines in ZZHPD by HPLC-FLD. Compared with the HP group, Tmax (time to reach peak drug concentration in plasma) and AUC(0-τ) significantly increased in the ZZHPD and HP-ZZ groups. There was little change in the HP-ZS group in comparison with the HP group, which indicated that ZZ promotes absorption extent and defers the absorption rate of MN. The different compatibility of ZZHPD had a different degree of impact on the concentration of MN and HN in brain. The concentration of MN significantly increased in the HP-ZZ group while it decreased in the HP-ZS group compared with the HP group, which explained the concentration of compounds being slightly greater in the ZZHPD group than in the HP group. HP mixed with other medicines resulted in a decrease in HN concentration in the brain, particularly HP compatible with ZS. The results could be helpful for revealing the compatibility mechanism and providing clinical medication guidance for ZZHPD.

Methanolic extract of Hypericum perforatum cells elicited with Agrobacterium tumefaciens provides protection against oxidative stress induced in human HepG2 cells

Hypericum perforatum L. (HP) is widely used in traditional medicine to treat several medical conditions since ancient times. In our group, this plant has been used for biotechnological production of bioactive phytochemicals. In the present study, the ability of a methanolic extract of HP cells elicited with Agrobacterium tumefaciens (AT) to induce intracellular antioxidant defenses of human HepG2 cells and to protect them against tert-butyl hydroperoxide-induced oxidative stress was tested. The elicited HP extract significantly prevented tert-butylhydroperoxide-induced cell death, glutathione (GSH) depletion, and DNA damage, in both pre- and co-incubation regimes, while the extract from control HP did not. When incubated alone, none of the extracts were cytotoxic or genotoxic. Interestingly, contrary to control HP extract, incubation of HepG2 cells with extract from elicited HP cells induced significantly GSH levels and several cytoprotective enzymes. These effects were associated with an increase of Nrf2 levels in nucleus, which may explain the cytoprotective action of the elicited HP extract in the pre-incubation regime. Taken together, our results suggest that elicitation of HP cells with AT is an interesting biotechnological approach for the production of cytoprotective and antioxidant compounds for pharmaceutical applications.

In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo

Hyperforin, a major constituent of St. John’s Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John’s Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H2DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC50 0.7μM corresponding to 0.42μg/ml) was much more effective compared to Trolox (EC50 12μg/ml) and N-acetylcysteine (EC50 847μg/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5%w/w of a hyperforin-rich HP extract was determined to be 200×1014 radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger.

Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model

Ethnopharmacological relevanceSince ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. Materials and methodsThe efficacy of 125, 250, and 500mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. ResultsThe rats’ weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. ConclusionMore studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment.

English

Obstructive nephropathy induced by urine reflux due to uroliths, prostatic hypertrophy and other disorders will result in renal interstitial fibrosis and inflammation. Because ofHypericum perforatums (HP) anti-oxidant and anti-inflammatory properties, the clinical usage of this drug in renal function has been studied. We divided 30 Sprague-Dawley rats randomly into 5 groups: sham group (Sham), untreated unilateral ureteral obstruction (UUO) group, vitamin E treated (50 IU/kg) UUO group, HP 30 and 60 treated (30 and 60 mg/kg) UUO groups. All of the chemicals were administrated 7 days before and after operation. At 7 days after UUO, blood samples were collected and left kidney were dissected and Haematoxylin and Eosin (HE) and Masson staining were used to study the dynamic histological changes. Low dose of HP similar to vitamin E alleviated the renal interstitial fibrosis, tubular cell degeneration, inflammatory cell infiltration and glomerular damage (p&lt;0.01) but high dose of HP increased injuries (p&lt;0.05). We provide for the first time evidence that HP extract in obstructed kidney has different effects, such that in low dose it can be affected as a renoprotective agent, but in high dose, it can be affected as an inflammation triggering substance. The demonstration of exact mechanism (s) of opposite effect of HP extracts needs more cellular and molecular investigations. &nbsp; Key words:&nbsp;Hypericum perforatum,&nbsp;renal glomerular damage, renal tubulointerstitial damage, unilateral ureteral obstruction.

Discriminant analysis to separate a study population by treatment subgroups in a pilot clinical trial with a new pentapeptide antidepressant (INN 00835)

Hyperforin, a major constituent of St. John’s Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John’s Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H2DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC50 0.7 μM corresponding to 0.42 μg/ml) was much more effective compared to Trolox (EC50 12 μg/ml) and N-acetylcysteine (EC50 847 μg/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5% w/w of a hyperforin-rich HP extract was determined to be 200 × 1014 radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger.

In Vitro Studies on the Interaction of Phytase with Trypsin and Amylase Extracted from Shrimp (Penaeus vannamei) Hepatopancreas

Phytases are added to livestock feeds to enhance bioavailability of phytate phosphorus. The possibility of adding phytase to shrimp feeds was investigated by studying the in vitro interaction of phytase on trypsin and amylase extracted from the hepatopancreas (HP extract) of Penaeus vannamei. Proteolysis of soybean meal (SBM) protein measured as tryptic activity increased linearly with increasing phytase units, indicating that phytase may exert an indirect but positive effect on SBM protein hydrolysis. Increase in tryptic hydrolysis was not significantly affected by changes in pH from 5.5 to 8.5. An additive effect was observed between trypsin and possibly other proteolytic enzymes in the HP extract and phytase on the release of phosphorus from phytate in SBM. An inhibitory effect on HP extract amylase activity by phytase, reported here for the first time, may have important implications on direct addition of phytase to shrimp feeds.