Neutraceuticals

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Neutraceuticals

March 4, 2015 by larryhbern

Neutraceuticals

Author and Curator: Larry H Bernstein, MD, FCAP

Introduction

This article is concerned with a very fast growing part of the food industry. Unfortunately, there have been such products that were sold that did not contain what was purported to provide the benefit. This segment of the medicinal industry is regulated as FOOD (food product), unlike pharmaceuticals. This means that the basic safety requirement is compliance with a labeling standard. There are no clinical trials. The incentive for the development in this sector is from 2,500 years of history in the use of plants for health benefits. The new science that can improve the potency and the safety is the technology that has grown up to extract, refine and produce the active substance in pure form. The methods used called Flow Chemistry has been covered recently by Anthony Melvin Crasso at his outstanding pharmaceutical site. I shall list important articles that have been in the Pharmaceutical Intelligence site at the end of this discussion.

Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.) decoction extract in rats

Hichem Sebai, Mohamed-Amine Jabri, Abdelaziz Souli, Kais Rtibi, et al.
J Ethnopharmacol 152(2014)327–332
http://dx.doi.org/10.1016/j.jep.2014.01.015

Ethnopharmacological relevance: Matricaria recutita L. (Chamomile) has been widely used in the Tunisian traditional medicine for the treatment of digestive system disorders. The present work aims to investigate the protective effects of chamomile decoction extract (CDE) against castor oil-induced diarrhea and oxidative stress in rats. Methods:The antidiarrheal activity was evaluated using castor oil-induced diarrhea method. In this respect, rats were divided into six groups: Control, Castor oil, Castor oil + Loperamide (LOP) and Castor oil + various doses of CDE. Animals were perorally (p.o.) pre-treated with CDE during 1 hand intoxicated for 2 or 4h by acute oral administration of castor oil. Results: Our results showed that CDE produced a signiﬁcant dose-dependent protection against castor oil-induced diarrhea and intestinal ﬂuid accumulation. On the other hand, we showed that diarrhea was accompagnied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level and depletion of antioxidant enzyme activities as superoxide dismutase(SOD), catalase (CAT) and glutathione peroxidase (GPx). Castor oil also increased gastric and intestinal mucosa hydrogen peroxide (H₂O₂) and free iron levels. Importantly, we showed that chamomile pre-treatment abrogated all these biochemical alterations. Conclusion: These ﬁndings suggested that chamomile extract had a potent antidiarrheal and antioxidant properties in rats conﬁrming their use in traditional medicine.

Anti-diarrheal activity of methanol extract of Santalum album L. in mice and gastrointestinal effect on the contraction of isolated jejunum in rats

Huimin Guo, Jingze Zhang, Wenyuan Gao, Zhuo Qu, Changxiao Liu
J Ethnopharmacol 54(2014)704–710
http://dx.doi.org/10.1016/j.jep.2014.04.043

Ethnopharmacological relevance: Santalum album L., namely Sandalwood, honoredas “Green Gold”, is a traditional Chinese herb which has the effects of antidiarrheal and antibacterial activity. But there is limited scientiﬁc study on its activity and mechanism in gastrointestinal disorders.
Materials and methods: in vivo, after intragastric administration, the methanol extract of Sandalwood (SE) (200, 400 and 800 mg/kg) were studied in castor oil-induced diarrhea mice. By the test of small intestinal hyperfunction induced by neostigmine, SE was studied on gastrointestinal transit including gastric emptying and small intestinal motility. Meanwhile, in vitro, the effects of SE (0.02, 0.05, 0.1, 0.2, 0.3, 0.4 mg/mL) on the isolated tissue preparations of rat jejunum were also investigated. The rat jejunum strips were precontacted with acetylcholine (Ach; 10^-6M), 5-hydroxytryptamine (5-HT, 200 μM) or potassium chloride (KCl; 60mM) and tested in the presence of SE. In addition, the possible myogenic effect was analyzed in the pretreatment of the jejunum preparations with SE or verapamilin Ca ²⁺-free high-K⁺ (60mM) solution containing EDTA. Results: At doses of 200, 400 and 800 mg/kg, SE showed signiﬁcant anti-diarrheal activity against castor oil-induced diarrhea as compared with the control. At the same doses, it also inhibited the gastric emptying and small intestinal motility in the mice of which small intestinal hyperfunction induced by neostigmine. It caused inhibitory effects on the spontaneous contraction of rat-isolated jejunum in dose-dependent manner ranging from 0.02 to 0.4 mg/mL, and it also relaxed the Ach-induced, 5-HT-induced andK⁺-induced contractions. SE shifted the Ca ²⁺concentration–response curves to right, similar to that caused by verapamil (0.025mM).
Conclusions: These ﬁndings indicated that SE played a spasmolytic role in gastrointestinal motility which was probably mediated through inhibition of muscarinic receptors, 5-HT receptors and calcium inﬂux. All these results provide pharmacological basis for its clinical use in gastrointestinal tract.

Apocynin attenuates isoproterenol-induced myocardial injury and ﬁbrogenesis

Li Liu, Jingang Cui, Qinbo Yang, Chenglin Jia, Minqi Xiong, et al.
Biochem Biophys Res Commun 449(2014)55–61
http://dx.doi.org/10.1016/j.bbrc.2014.04.157

Oxidative stress is mechanistically implicated in the pathogenesis of myocardial injury and the subsequent ﬁbrogenic tissue remodeling. Therapies targeting oxidative stresss in the process of myocardial ﬁbrogenesis are still lacking and thus remain as an active research area in myocardial injury management. The current study evaluated the effects of a NADPH oxidase inhibitor, apocynin, on the production of reactive oxygen species and the development of myocardial ﬁbrogenesis in isoproterenol (ISO)-induced myocardial injury mouse model. The results revealed a remarkable effect of apocynin on attenuating the development of myocardial necrotic lesions, inﬂammation and ﬁbrogenesis. Additionally, the protective effects of apocynin against myocardial injuries were associated with suppressed expression of an array of genes implicated in inﬂammatory and ﬁbrogenic responses. Our study thus provided for the ﬁrst time the histopathological and molecular evidence supporting the therapeutic value of apocynin against the development of myocardial injuries, in particular, myocardial ﬁbrogenesis, which will beneﬁt the mechanism-based drug development targeting oxidative stress in preventing and/or treating related myocardial disorders.

Anti-tumor effect of Shu-gan-Liang-Xue decoction in breast cancer is related to the inhibition of aromatase and steroid sulfatase expression

Ning Zhou, Shu-Yan Han, Fei Zhou, Ping-ping Li
J Ethnopharmacol 154 (2014) 687–695
http://dx.doi.org/10.1016/j.jep.2014.04.045

Ethnopharmacological relevance: Shu-Gan-Liang-Xue Decoction (SGLXD), a traditional Chinese herbal formula used to ameliorate the hot ﬂushes in breast cancer patients, was reported to have anti-tumor effect on breast cancer. Estrogen plays a critical role in the genesis and evolution of breast cancer. Aromatase and steroid sulfatase (STS) are key estrogen synthesis enzymes that predominantly contribute to the high local hormone concentrations. The present study was to evaluate the anti-tumor effect of SGLXD on estrogen receptor (ER) positive breast cancer celllineZR-75-1, and to investigate its underlying mechanisms both in vitro and in vivo.
Materials and methods: The anti-tumor activity of SGLXD in vitro was investigated using the MTT assay. The in vivo anti-tumor effect of SGLXD was evaluated in non-ovariectomized and ovariectomized athymic nude mice. The effect of SGLXD on enzymatic activity of aromatase and STS was examined using the dual-luciferase reporter (DLR) based on bioluminescent measurements. Aromatase and STS protein level were assessed using Western blot assay. Results: SGLXD showed dose-dependent inhibitory effect on the proliferation of ZR-75-1 cells with IC50 value of 3.40 mg/mL. It also suppressed the stimulating effect on cell proliferation of testosterone and estrogen sulfates (E1S). Oral administration of 6 g/kg of SGLXD for 25 days resulted in a reduction in tumor volume in non-ovariectomized and ovariectomized nude mice. The bioluminescent measurements conﬁrmed that SGLXD has a dual-inhibitory effect on the activity of aromatase and STS. Western blot assay demonstrated that the treatment of SGLXD resulted in a decrease in aromatase and STS protein levels both in vitro and in vivo. Conclusion: Our results suggested that SGLXD showed anti-tumor effect on breast cancer cells both in vitro and in vivo. The anti-tumor activity of SGLXD is related to inhibition of aromatase and STS via decreasing their expression. SGLXD may be considered as a novel treatment for ER positive breast cancer.

Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: Possible involvement of mitochondrial dysfunction and apoptosis

Bidya Dhar Sahu, Harika Anubolu, Meghana Koneru, et al.
Life Sciences 107 (2014) 59–67
http://dx.doi.org/10.1016/j.lfs.2014.04.035

Aims: Preventive and/or therapeutic interventions using natural products for ischemic heart disease have gained considerable attention world wide. This study investigated the cardioprotective effect and possible mechanism of embelin, a major constituent of EmbeliaribesBurm, using isoproterenol (ISO)-induced myocardial infarction model in rats.
Materials and methods: Rats were pretreated for three days with embelin (50mg/kg,p.o) before inducing myocardial injury by administration of ISO (85mg/kg) subcutaneously at aninterval of 24h for 2 consecutive days. Serum was analyzed for cardiac speciﬁc injury biomarkers, lipids and lipoprotein content. Heart tissues were isolated and were used for histopathology, antioxidant and mitochondrial respiratory enzyme activity assays and western blot analysis. Key ﬁndings: Results showed that pretreatment with embelin signiﬁcantly decreased the elevated levels of serum speciﬁc cardiac injury biomarkers (CK-MB, LDH and AST), serum levels of lipids and lipoproteins and histopathological changes when compared to ISO-induced controls. Exploration of the underlying mechanisms of embelin action revealed that embelin pretreatment restored the myocardial mitochondrial respiratory enzyme activities (NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity), strengthened antioxidant status and attenuated ISO-induced myocardial lipid peroxidation. Immunoblot analysis revealed that embelin interrupted mitochondria dependent apoptotic damage by increasing the myocardial expression of Bcl-2 and downregulating the expression of Bax, cytochrome c, cleaved-caspase-3&9 and PARP. Histopathology ﬁndings further strengthened the cardioprotective ﬁndings of embelin. Signiﬁcance: Result suggested that embelin may have a potential beneﬁt in preventing ischemic heart diseasel like myocardial infarction.

Effect of Matricaria chamomilla L. ﬂower essential oil on the growth and ultrastructure of Aspergillus niger vanTieghem

Marziyeh Tolouee, Soheil Alinezhad, Reza Saberi, Ali Eslamifar, et al.
Intl J Food Microbiol 139 (2010) 127–133
http://dx.doi.org:/10.1016/j.ijfoodmicro.2010.03.032

The antifungal activity of Matricaria chamomilla L. ﬂower essential oil was evaluated against Aspergillus niger with the emphasis on the plant’s mode of action at the electron microscopy level. A total of 21 compounds were identiﬁed in the plant oil using gaschromatography/massspectrometry(GC/MS) accounting for 92.86% of the oil composition. The main compounds identiﬁed were α-bisabolol (56.86%), trans-trans-farnesol (15.64%), cis-β-farnesene (7.12%), guaiazulene (4.24%), α-cubebene (2.69%), α-bisabololoxideA (2.19%) and chamazulene (2.18%). In the bioassay, A.niger was cultured on Potato Dextrose Broth medium in 6-well microplates in the presence of serial two fold concentrations of plant oil (15.62 to 1000 µg/mL) for 96h at 28°C. Based on the results obtained, A. niger growth was inhibited dose dependently with a maximum of ∼92.50% at the highest oil concentration. A marked retardation in conidial production by the fungus was noticed in relation to the inhibition of hyphal growth. The main changes of hyphae observed by transmission electron microscopy were disruption of cytoplasmic membranes and intracellular organelles, detachment of plasma membrane from the cell wall, cytoplasm depletion, and completed is organization of hyphal compartments. In scanning electron microscopy, swelling and deformation of hyphal tips, formation of short branches, and collapse of entire hyphae were the major changes observed. Morphological alterations might be due to the effect on cell permeability through direct interaction of M. chamomilla essential oil with the fungal plasma membrane. These ﬁndings indicate the potential of M. chamomilla L. essential oil in preventing fungal contamination and subsequent deterioration of stored food and other susceptible materials.

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