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Pharmacognostic and pharmacological profile of Humulus Lupulus L.
The present review describes the morphological, phytochemical and ethnopharmacological aspects of Humulus lupulus L. (Cannabinaceae) and summarizes the most interesting findings obtained in the preclinical and clinical research related to the plant. The female inflorescences of Humulus lupulus (hops), well-known as bittering agent in brewing industry, have long been used in traditional medicine mainly to treat sleep disturbances. However the sedative activity is still under investigation in order to recognize the active principles responsible for the neuropharmacological effects observed in laboratory animals, and their mechanism of action. Here we report the data from our experiments as well as those obtained from other researchers, focusing on the variability of the results. Other traditional applications of hops as stomachic, antibacterial and antifungal remedy have been supported by in vivo and/or in vitro investigations. In recent years some prenylated chalcones present in hops have received much attention for their biological effects: in particular, xanthohumol has been shown to exert cancer chemopreventive activity in in vitro experiments, while 8-prenylnaringenin has been characterized as one of the most potent phytoestrogens isolated until now. Nevertheless much additional work is needed to open up new biomedical application of these compounds
Role of ferutinin in the impairment of female sexual function induced by Ferula hermonis
In the present study, we evaluated the effects of single components of Ferula hermonis extract on female rat sexual behaviour. Ovariectomized rats hormonally primed with estradiol benzoate (1.5 or 10 mu g/rat s.c.) and progesterone (500 mu g/rat s.c.) were acutely treated by oral gavage with ferutinin, teferin and teferdin (2.5 mg/kg). Thereafter they were tested for: a) partner preference, b) receptivity, c) proceptivity, d) paced mating behaviour. In the partner preference test, the choice of the female for a sexually active male was not influenced by the different treatments. Similarly, during the paced mating test, the contact-return latencies as well as the percentage of exits from the male compartment were not different in control and treated rats. Therefore none of the three compounds showed the capacity to alter sexual motivation. On the other hand, ferutinin, but not teferin and teferdin, significantly inhibited female receptivity. These results suggest a primary role of ferutinin in the impairment of sexual behaviour elicited by F hermonis extract in hormone primed-female rats
Neuropharmacological activity of Humulus lupulus L.
The traditional use of hops in the treatment of sleep disturbances has been supported by experimental studies performed in rodents, as described in the present chapter. An inhibitory influence on the central nervous system was suggested by the finding of a reduction in locomotor behavior together with an enhancement of pentobarbital hypnotic activity, following the oral administration of hop extracts. A lipophilic hop extract showedan antidepressant-like activity in an animal model of behavioral despair, without a significant anxiolytic activity. Among hop components, the bitter acids have been carefully investigated for their role in the neuropharmacological activities of hops. In particular, the fraction containing alfa -acids has been recognizedto be mainly responsible for the sedative effects of hops. On the other hand the fraction containing beta -acids appears to exert a central stimulatory activity, probably due to a reduction in the GABAergic activity. This hypothesis is supported by its effects in animal models of sedation and convulsions as well as in electrophysiological studies on cerebellar granule cells in culture.Clinical trials specifically related to the sedative properties of hops are still inadequate since human studies were mainly performed using valerian–hop combination extracts
The phytoestrogen ferutinin affects female sexual behavior modulating ERα expression in the hypothalamus
This study was designed to assess the effect of the phytoestrogenic compound ferutinin, chronically administered in ovariectomized progesterone primed rats, alone or in combination with estradiol benzoate. After 2, 3 and 4 weeks of treatments, female rats were tested for receptive (lordosis) and proceptive behaviors (hops, darts and ear wigglings). Ferutinin given alone markedly increased the intensity of the lordotic response in ovariectomized rats but failed to significantly affect proceptivity. On the other hand estradiol benzoate significantly increased both receptive and proceptive behaviors. When administered in combination with estradiol, ferutinin reduced the increase in receptivity and proceptivity due to estrogen effects, acting as an antiestrogen. At the end of the behavioral experiments, animals were sacrificed and Western blot analysis of estrogen receptor α (ERα) levels was performed in the dissected hypothalami. Ferutinin increased ERα expression when administered alone, as estradiol did, but decreased the response to estradiol when administered in combination. These results suggest that ferutinin displays estrogenic or antiestrogenic activity through ERα in the hypothalamus, depending on the absence or the presence of estrogen primin
Influence of Eurycoma longifolia on the copulatory activity of sexually sluggish and impotent male rats
AIM OF THE STUDY: The root of Eurycoma longifolia Jack, native to South East Asia, has long been used as a male aphrodisiac remedy to treat sexual disorders. In the study we evaluated the influence of Eurycoma longifolia Jack on sexual behavior (including both motivation and copulatory performance) of sexually sluggish and impotent male rats. MATERIALS AND METHODS: The root powder of the plant was orally administered to adult Sprague-Dawley male rats, classified as sexually sluggish or impotent taking in account their behavior in pre-experimental tests. Groups of 8 animals each were submitted to three different types of treatment: (1) acute at 3 dose levels (250, 500 and 1000 mg/kg); (2) subacute (daily for 6 days) at the dose of 500 mg/kg and (3) subchronic (daily for 12 days) at the same dose (500 mg/kg). Mount, intromission and ejaculation latencies and post-ejaculatory interval were recorded during the mating test in order to evaluate sexual performance. In addition the partner preference test was used to assess sexual motivation. Testosterone serum levels were measured in subacutely treated rats and compared with the values of controls receiving vehicle. RESULTS: Concerning the copulatory activity of sexually sluggish rats, both acute (dosed at 500 and 1000 mg/kg) and subacute treatments with the root powder significantly reduced ejaculation latencies, increasing also the percentage of mounting and ejaculating animals; in addition the subacute administration reduced post-ejaculatory interval. In impotent rats both subacute and subchronic treatments increased the percentage of mounting and ejaculating rats. The motivational behavior of sluggish rats during the partner preference test was not affected by the treatments. Testosterone serum levels were increased in rats subacutely treated in comparison with controls. CONCLUSION: Eurycoma longifolia root improved sexual performance but not motivation in sluggish rats after acute or subacute administration. The effect could be mainly ascribed to increased testosterone levels
Further Evidence of the Antiulcer Activity of IAC, a Novel Free Radical Scavenger
It has been proposed that free radicals, reactive oxygen species (ROS) and reactive nitrogen species play a critical role in gastric mucosal damage. It is well known that the exposure of gastric mucosa to damaging factors such as stress and nonsteroidal anti-inflammatory drugs produces acute ulcers that are mainly mediated by ROS. The aim of the present study was to investigate the gastroprotective properties of bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC), a novel nonpeptidyl low-molecular-weight radical scavenger, in two different models of gastric ulcer in rats caused by ROS. IAC was orally administered at the doses of 50 and 100 mg/kg before gastric ulceration induced by indomethacin and water immersion and restraint stress. The number and severity of gastric lesions, following macroscopic inspection of the mucosa, were evaluated and expressed as an ulcer score. Oral administration of IAC dosed at 50 and 100 mg/kg was able to significantly prevent gastric ulceration induced by indomethacin and by stress. The gastroprotective effect of IAC on gastric mucosa could be attributed to its intrinsic antioxidant activity, suggesting it as a novel antiulcer agent. Copyright (C) 2011 S. Karger AG, Base
Anti-ulcer activity of IAC, a novel free-radical scavenger, in rats.
Objectives We investigated the ability of a novel low-molecular-weight free-radical scavenger, bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), to protect the gastric mucosa from indometacin-induced ulceration.Methods The pharmacological effects of IAC, administered orally or by intraperitoneal injection, on the gastric mucosa were assessed in a rat model of gastric ulceration induced by indometacin. The effect of IAC on the level of prostaglandin PGE2 in the gastric mucosa was also investigated. Results IAC, which has no ulcerative activity per se, had a preventive and protective activity against indometacin-induced gastric ulceration. This effect could be only partially attributed to a modulatory effect of IAC on PGE2 levels; it is more likely to be due to the antioxidant activity of the compound. Conclusions Taking into account the properties of IAC and the mechanisms underlying gastric inflammation elicited by non-steroidal anti-inflammatory drugs, IAC may represent a novel anti-ulcer agent
New insight in the neuropharmacological activity of Humulus lupulus L
The purpose of the present study was to investigate the effects of Humulus lupulus CO2 extract and its fraction containing α-acids on the central nervous system of rats. Both tested substances were able to prolong pentobarbital sleeping time, without affecting the latency to the loss of the righting reflex. This effect was dose-dependent, starting from a minimal dose of 10 mg/kg. Neither the extract nor its α-acid fraction affected the locomotor activity in the open field test or exerted an anxiolytic effect in rats submitted to the elevated plus-maze test. Interestingly both compounds reduced the immobility time during the behavioral despair test when administered three times (24, 5 and 1 h) before the test. In conclusion this report shows that Humulus lupulus CO2 extract exerts: (a) a pentobarbital sleep-enhancing property without influencing the motor behavior of rats; (b) an antidepressant activity. The same effects were elicited by the administration of the Humulus lupulus fraction containing α-acids, which can be considered as the major responsible for the enhanced pentobarbital effect and for the antidepressant property
Ferula hermonis impairs sexual behavior in hormone-primed female rats
The influence of Ferula hermonis root extract on sexual behavior was studied in female rats. Sexual receptivity, proceptivity and paced mating behavior were evaluated in ovariectomized females primed with estradiol benzoate (EB) and progesterone (P) and then treated with F hermonis extract acutely (30 and 60 mg/kg) or subehronically (1 and 10 mg/kg daily for 10 consecutive days). A significant reduction in lordosis responses was observed in rats after acute (60 mg/kg) or subehronic (1 and 10 mg/kg) administration of the plant extract. Similarly, a decrease in proceptive behaviors was exhibited by F hermonis treated rats in comparison with EB + P controls. No difference was found in the patterns of paced mating behavior between control and treated animals. The present results demonstrate that the acute or repeated ingestion of F hermonis specifically impairs the receptive and proceptive components of female sexual behavior. The effect could be the consequence of an antiestrogenic action of the extract in hormone-primed female rats
The phytoestrogen ferutinin improves sexual behavior in ovariectomized rats
The present study was designed to examine the effect of ferutinin chronic administration on sexual behavior of ovariectomized non-estrogen-primed rats. Starting from 3 weeks after ovariectomy, female rats were orally treated with ferutinin at the doses of 0.2 and 0.5mg/kg, daily for 4 weeks. Ferutinin's effect was compared with that of estradiol benzoate, subcutaneously injected at the dose of 1.5mug/rat twice a week. Animals were tested for sexual motivation, receptivity and proceptivity after 1, 2 and 3 weeks of treatment and for paced mating behavior after 4 weeks of treatment. Before each experimental test, they received progesterone injection (500mug/rat). Both dosages of ferutinin significantly increased the receptive behavior in a time-dependent manner, as well as estradiol benzoate did. Also proceptive behaviors increased in ferutinin-treated animals in comparison with control ones. During the partner preference test ferutinin was able to induce a significant preference for a sexually active male over a sexually receptive female. Moreover, ferutinin restored a normal paced mating behavior, which had been suppressed by ovariectomy. These results show that ferutinin exerts an estrogenic activity in ovariectomized non-estrogen-primed female rats
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