Polyphenols from Ginkgo biloba

By Sephadex LH-20 gel chromatography of an extract from Gingko biloba leaves, polymeric proanthocyanidins were eluted after the fractions of flavonol glycosides and biflavone glycosides. A purified proanthocyanidin polymer accounted for 86.6% of the total proanthocyanidins, and for 37.7% of the total antioxidant activity of this leaf extract. For structure elucidation, the polymer was submitted to acidic depolymerization in the presence of phloroglucinol. The structures of the resulting flavan-3-ols and phloroglucinol adducts were determined on the basis of 1D-and reverse 2D-NMR (HSQC, HMBC) spectra of their peracetylated derivatives, MALDI-TOF-MS and CD-spectroscopy. The observations resulting from the degradation with phloroglucinol were confirmed by 13C-NMR spectroscopy of the polymer. The mean molecular weight of the polymeric fraction was estimated to be 9–10 flavan-3-ol-units

DETERMINATION OF HYDROLYSIS PARAMETERS OF YOHIMBINE HCl AT NEUTRAL AND SLIGHTLY ACIDIC MEDIUM

Objectives: In the process of investigating various new drug delivery systems of yohimbine HCl (Yoh), it was necessary to study some of the physical chemical properties of the drug including its stability at neutral, acidic and slightly acidic conditions.Methods: A validated HPLC method was developed and employed for analysis of Yoh containing solutions. The mobile phase composed of 60% menthol: 40% NaOAc (%v/v), and Gemi C18 column, 5 µm particle size was used as a stationary phase. The degradation product was found to be yohimbinic acid (YA). The retention times for Yoh and YA were 5 and 3 minutes, respectively. This study investigated the kinetics of hydrolysis of Yoh at pH 6.0 and 7.0 at temperatures from 50 °C to 80 °C.Results: The reaction followed first order kinetics and the activation energy ∆E of the reaction at pH 6 and pH 7 was found to be 16.2 and 16.8 Kcal. mole-1, respectively. While the values of A were found to be 41.8 and 44.1 Kcal. mole-1 at pH 6 and 7, respectively. The pseudo first order rate constants (K) at pH 6 and 7 were calculated as 2.76 Ñ… 10 -3 h-1 and 3.42 Ñ… 10 -3 h-1, respectively.Conclusion: Such results indicate high stability of the drug at these pH values. At highly acidic medium the reaction was found to be extremely slow indicating the absence of acid catalysis on the hydrolysis of Yoh. Thus, the yohimbine ester group resists hydrolysis in highly acidic conditions.Â

Impact of Pomegranate Juice on the Pharmacokinetics of CYP3A4- and CYP2C9-Mediated Drugs Metabolism: A Preclinical and Clinical Review

The Punica granatum L. (pomegranate) fruit juice contains large amounts of polyphenols, mainly tannins such as ellagitannin, punicalagin, and punicalin, and flavonoids such as anthocyanins, flavan-3-ols, and flavonols. These constituents have high antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, and anticancer activities. Because of these activities, many patients may consume pomegranate juice (PJ) with or without their doctor’s knowledge. This may raise any significant medication errors or benefits because of food-drug interactions that modulate the drug’s pharmacokinetics or pharmacodynamics. It has been shown that some drugs exhibited no interaction with pomegranate, such as theophylline. On the other hand, observational studies reported that PJ prolonged the pharmacodynamics of warfarin and sildenafil. Furthermore, since it has been shown that pomegranate constituents inhibit cytochrome P450 (CYP450) activities such as CYP3A4 and CYP2C9, PJ may affect intestinal and liver metabolism of CYP3A4 and CYP2C9-mediated drugs. This review summarizes the preclinical and clinical studies that investigated the impact of oral PJ administration on the pharmacokinetics of drugs that are metabolized by CYP3A4 and CYP2C9. Thus, it will serve as a future road map for researchers and policymakers in the fields of drug-herb, drug-food and drug-beverage interactions. Preclinical studies revealed that prolonged administration of PJ increased the absorption, and therefore the bioavailability, of buspirone, nitrendipine, metronidazole, saquinavir, and sildenafil via reducing the intestinal CYP3A4 and CYP2C9. On the other hand, clinical studies are limited to a single dose of PJ administration that needs to be protocoled with prolonged administration to observe a significant interaction

A Functional Food Mixture “Protector” Reinforces the Protective Immune Parameters against Viral Flu Infection in Mice

Background: Viral influenza infection causes serious health issues especially when an outbreak occurs. Although influenza virus vaccines are available and each year manufactures modify the vaccine depending on the expected mutated strain, it is still far from satisfactory, mainly in young children and older adults. Therefore, a product that can support and shape the immune system to protect against viral flu infections is highly essential. Methods: A functional food water-soluble mixture of pomegranate, red grape, dates, olive fruit, figs, and ginger extracts, termed herein “Protector”, was prepared and tested in stimulating/modulating the production of specific cytokines, and hemagglutinin inhibition (HAI) antibodies following viral flu vaccination in mice. Results: A single intraperitoneal or multiple oral administration for 1–7 days of “Protector” significantly increased the production of interferon (IFN)-γ and interleukin (IL)-12 in blood, spleen, and lungs of mice. When “Protector” was orally administered for one week following a single vaccine injection (primary immunization) or for two weeks (one week apart) following double vaccine injections (secondary immunization), mice significantly produced higher titers of HAI antibodies. This increase in HAI antibodies was associated with Pillow-inducing significant and different changes in vaccine-induced IFN-γ, IL-12, IL-6 and IL-22 following primary and secondary immunizations. Conclusions: “Protector” administration reinforces the protective immune parameters against viral flu infection. Therefore, after performing preclinical toxicology studies and ensuring its safety, “Protector” should be considered a potential product to be tested in clinical trials to conclude its efficacy in reducing the devastating effects of flu infection in humans and its outbreaks

Stability Study and a 14-Day Oral Dose Toxicity in Rats of Plantain Leaf Extract (Plantago lanceolata L.) Syrup

Plants have been used since antiquity to treat and prevent diseases. Plantain (Plantago lanceolata L.) is traditionally used for the treatment of the common cold and associated symptoms such as cough. This study was designed to evaluate the oral toxicity of plantain leaf extract-containing syrup. In preparation of the toxicological examination and to ensure the quality of the herbal preparation, analytical methods were developed and validated, and stability testing was performed. Physicochemical and microbial quality, thin layer chromatography patterns and high performance liquid chromatography fingerprints complied with the specifications during the entire period of stability testing. The marker substance, acteoside, remained within the stability-defining limits of 90%–110% for quantitative determinations. No hint of toxicity emerged from 14-day repeat dose toxicity testing in rats. The animals were given doses of 3, 6, or 12 mL of syrup per kg body weight by gavage twice daily. All animals showed normal appearance and behavior. Body and organ weights at the end of the study were similar to those in the control group. Overall, P. lanceolata syrup was found to be stable and non-toxic under the test conditions

A Functional Food Mixture “Protector” Reinforces the Protective Immune Parameters against Viral Flu Infection in Mice

Background: Viral influenza infection causes serious health issues especially when an outbreak occurs. Although influenza virus vaccines are available and each year manufactures modify the vaccine depending on the expected mutated strain, it is still far from satisfactory, mainly in young children and older adults. Therefore, a product that can support and shape the immune system to protect against viral flu infections is highly essential. Methods: A functional food water-soluble mixture of pomegranate, red grape, dates, olive fruit, figs, and ginger extracts, termed herein “Protector”, was prepared and tested in stimulating/modulating the production of specific cytokines, and hemagglutinin inhibition (HAI) antibodies following viral flu vaccination in mice. Results: A single intraperitoneal or multiple oral administration for 1–7 days of “Protector” significantly increased the production of interferon (IFN)-γ and interleukin (IL)-12 in blood, spleen, and lungs of mice. When “Protector” was orally administered for one week following a single vaccine injection (primary immunization) or for two weeks (one week apart) following double vaccine injections (secondary immunization), mice significantly produced higher titers of HAI antibodies. This increase in HAI antibodies was associated with Pillow-inducing significant and different changes in vaccine-induced IFN-γ, IL-12, IL-6 and IL-22 following primary and secondary immunizations. Conclusions: “Protector” administration reinforces the protective immune parameters against viral flu infection. Therefore, after performing preclinical toxicology studies and ensuring its safety, “Protector” should be considered a potential product to be tested in clinical trials to conclude its efficacy in reducing the devastating effects of flu infection in humans and its outbreaks

Eriobotrya japonica Water Extract Characterization: An Inducer of Interferon-Gamma Production Mainly by the JAK-STAT Pathway

Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were performed on the water extract to investigate specific cytokines’ modulation. These earlier studies, however, have shown that EJ leaf water extract (WE) and the water phase (WP) induce cytokines’ production in in vitro and in vivo models. Therefore, the aim of this study was to specify the group(s) of compounds in EJ leaves that have this immunomodulatory activity and their mechanism of action. WE was obtained from boiling the leaves followed by butanol extraction, yielding a butanol-water phase (WP). WP was then subjected to methanol:acetone fractionation, yielding upper (MAU) and lower (MAL) phases. For further fractionation, MAU was subjected to column chromatography followed by elution with ethanol:water (EW), methanol:ethanol (ME) and, lastly, acetone:water (AW), respectively, to reveal three sub-fractions; MAU-EW, MAU-ME and MAU-AW. MAU-AW significantly increased IFN-γ production from unstimulated and stimulated mouse spleen cells, as well as CD3+ T cells and natural killer cells. Furthermore, the fold increase of IFN-γ production by MAU-AW was concentration dependent, higher than the parent extract or any of the other sub-fractions, and such an IFN-γ increase was reversed by two JAK-STAT inhibitors. In addition, MALDI-TOF-MS analysis of the extracts and sub-fractions showed compounds with molecular weights of >500 Daltons. The MAU-AW sub-fraction contained more polar compounds, such as flavonol and caffeic glycosides. In conclusion, these polar compounds in the EJ extract are responsible for inducing IFN-γ production. Further chemical elucidation is warranted to lead to a specific IFN-γ inducer and an immunomodulator in polarizing immune cells and balancing immune responses in certain diseases