Quantitative ethnomedicinal study and conservation status of medicinal flora used by the indigenous peoples of Sultan Khail valley, Dir Upper, Pakistan.

The present study was conducted to explore the ethnomedicinal uses, quantitative analysis and conservation status of medicinal flora of Sultan Khail valley, Dir Upper, Pakistan. The data was collected during 2017-2019 using a semi-structured questionnaire. Ethnomedicinal uses of plant species were determined and the plant species were classified based on habits, parts used, and method of preparation of remedies. Frequency of citation (FC), relative frequency of citation (RFC) and family importance values (FIV) were calculated. The plant species were assessed for their conservation status as per IUCN standard criteria. The inhabitants of the Sultan Khail valley use 88 plant species belonging to 57 families for the treatment of different human diseases. Lamiaceae was the dominant family represented with 8 medicinal species (9%) followed by Rosaceae (5 species, 6%). The most commonly used plant parts were leaves (33.1%) followed by fruits (16.1%), while the main method of remedy preparation was decoctions (33.3%). The highest RFC value was recorded for Geranium wallichianum (0.47), followed by Berberis lycium (0.44). Lamiaceae was the most cited family (FIV, 231), followed by Polygonaceae (73). Five plant species were found to be endangered, 39 species were vulnerable, 32 species were rare, and 12 species were found to be infrequent. The medicinal flora of the area is under severe biotic pressure and needs proper conservation; otherwise, they will be lost in the near future.

Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model.

BACKGROUND: Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. METHODS: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. RESULTS: Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. CONCLUSIONS: These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. SIGNIFICANCE: Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the effectiveness potential of a topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the chronic constriction injury-induced neuropathic pain model.

Preclinical profile of bacopasides from Bacopa monnieri (BM) as an emerging class of therapeutics for management of chronic pains.

Chronic pains management costs billions of dollars in medical exchequer to the world population. Additionally, 77% of people with chronic pains also have a degree of medically treatable depression. Opioids have a narrower safety index due to their side effects associated with its tolerance, hyperalgesia and subsequent dependence. Likewise, non steroidal anti-inflammatory drugs and anticonvulsants, also have limited safety and tolerability profile in the management of chronic pains. Bacopa monnieri, a renowned ayurvedic medicine has a strong antidepressant effect and significant antinociceptive effect, which is comparable to the effect of morphine via adenosinergic, opioidergic, and adrenergic mechanisms. BM has been also reported to be effective in neuropathic pains. Additionally, it has a strong anti-inflammatory effect mediated via COX-2 inhibitory mechanism. Apart from its effect of augmenting morphine analgesia, BM also inhibits opioid-withdrawal induced hyperalgesia, and acquisition and expression of morphine tolerance. BM is reported to have a strong protective effect against toxic effects of opiates on major organs like brain, kidneys and heart. BM is well documented to be safe and well tolerated herbal therapy in multiple clinical trials including various age groups. This minireview evaluated the preclinical data that highlights potential of BM as a future candidate for clinical management of chronic pains.

Total anti-oxidant status: a biochemical predictor of human male fertility.

The objective of the study was to assess whether seminal plasma total antioxidant status (TAS) can be used as a biochemical predictor of male fertility and its variation in different categories of infertile male subjects in our population. The study population consisted of 28 fertile and 127 infertile [teratozoospermic (30), asthenoteratozoospermic (30), azoospermic (21), oligoastheno-teratozoospermic (20), polyzoospermic (15) and oligozoospermic (11)] male subjects. Seminal plasma was separated by centrifugation and stored at minus 80 degree Celsius. Semen was analysed using computer-assisted semen analysis according to WHO criteria. Seminal plasma TAS was estimated by colorimetric method using Randox total antioxidant status kit. TAS of fertile male subjects was significantly (P < 0.001) higher than that of infertile patients. In whole studied population, seminal plasma TAS showed a significant positive correlation with sperm concentration (P < 0.001), sperm motility (P < 0.0001), and spermatozoa with normal morphology (P < 0.0001). In conclusion, this study suggests that TAS of seminal plasma is one of the important factors contributing to male infertility, and it can be used as a biochemical predictor for male fertility.

Antagonism of antinociceptive effect of hydro-ethanolic extract of Hypericum perforatum Linn. by a non selective opioid receptor antagonist, naloxone.

Hydro-ethanolic crude extract of Hypericum perforatum Linn. family hypericaceae (St. John's Wort) aerial parts (Hp. Cr) was studied for its possible antinociceptive effect against acetic acid-induced abdominal constriction assay in mice. Hp. Cr (10-20 mg kg(-1)), opium (10-30 mg kg(-1)), morphine (0.75-3.0 mg kg(-1)) and aspirin (50-100 mg kg(-1)) showed dose-dependent antinociceptive effect. In animals treated with naloxone (0.5 mg kg(-1)), the antinociceptive effect of Hp. Cr was significantly reduced similar to that of opium, while effect of aspirin remained unchanged. These results suggest that the antinociceptive effect of Hypericum perforatum may be mediated through activation of opioid receptors.

Do antidepressants affect motivation in conditioned place preference?

The positive motivational effects of a range of antidepressants/neurotransmitter reuptake inhibitor compounds were studied using conditioned place preference. These agents included amitriptyline (2.5-10 mg/kg), venlafaxine (5 and 10 mg/kg), sibutramine (5 and 10 mg/kg), fluoxetine (2.5-10 mg/kg), paroxetine (5-15 mg/kg) and sertraline (2.5-10 mg/kg). Male Wistar rats were place conditioned in a three-compartment box to vehicle or drug alternately for 8 days using a 30-min pretreatment time. Control animals received vehicle only. Cocaine (5 mg/kg) was used as a positive control for the procedure. Significant place preference (P<0.05) was observed with paroxetine (15 mg/kg), fluoxetine (5 and 10 mg/kg), sertraline (2.5-10 mg/kg) and cocaine. Venlafaxine and sibutramine, serotonin/noradrenaline reuptake inhibitors, produced no place conditioning, while the highest dose of the tricyclic antidepressant, amitriptyline (10 mg/kg), produced signs of place aversion. The role of serotonin in reward pathways and differences in serotonin, noradrenaline and dopamine reuptake-inhibiting properties of these compounds may explain why only the serotonin-selective reuptake inhibitors produced place preference in this study.

Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have discriminative stimulus properties.

The systemically active mixed inhibitor of enkephalin metabolism, N-((S)-2-benzyl-3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benzylester (RB 120), alone or in combination with 4-¿[2-[[3-(1H-indol-3-yl))-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1. ]dec-2-yloxy) carbonyl]amino¿propyl]amino]-1-phenylethyl]amino¿-4-oxo-[R-(R*, R*)]-butanoate N-methyl-D-glucamine (CI 988; CCK(1) receptor antagonist) was investigated for discriminative and morphine generalisation effects using an operant drug discrimination paradigm in rats. Animals dosed with RB 120 (10 mg/kg) failed to develop a discriminative response. Combined CI 988 (0.3 mg/kg) and RB 120 (10 mg/kg) also failed to elicit a discriminative response. Morphine-trained animals (3.0 mg/kg) did not generalise to RB 120 (10 and 20 mg/kg). Similarly, subsequent retraining of the same animals with 1.5 mg/kg of morphine did not elicit generalisation to RB 120 (10 or 20 mg/kg). Combined RB 120 (10 or 20 mg/kg) and CI 988 (0.3 or 3.0 mg/kg) treatment produced no notable drug lever selection in rats able to discriminate morphine (1.5 mg/kg) from saline. These results suggest that RB 120 may have low abuse potential at analgesic doses.

Potentiation of opioid-induced conditioned place preference by the selective serotonin reuptake inhibitor fluoxetine.

The ability of the selective serotonin reuptake inhibitor, fluoxetine, to modify the effects of morphine, N-((S)-2-benzyl-3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benzylester (RB 120; mixed inhibitor of enkephalin metabolism), and 4-¿[2-[[3-(1H-indol-3-yl))-2-methyl-1-oxo-2-[[(tricyclo[3,3,1,1] dec-2-yloxy) carbonyl] amino¿ propyl] amino]-1-phenylethyl] amino¿-4-oxo-[R-(R*,R*)]-butanoate N-methyl-D-glucamine (CI 988; cholecystokinin receptor subtype [CCK(2)] antagonist), was assessed using conditioned place preference. RB 120 and morphine both induced significant, dose-dependent conditioned place preference, whilst CI 988 failed to elicit conditioned place preference. A subthreshold dose of fluoxetine (2.5 mg/kg) potentiated the morphine submaximal response. Notably, the combination of a subthreshold dose of fluoxetine (2.5 mg/kg) with RB 120 (5 mg/kg) or CI 988 (3 mg/kg) was devoid of any significant conditioned place preference properties. Fluoxetine may act via enhanced serotonergic activity to modulate enkephalinergic tone. Agents that increase enkephalinergic tone more directly such as RB 120 and CI 988, at submaximal doses, did not induce conditioned place preference when co-administered with fluoxetine. These data suggest that fluoxetine, in combination with CI 988 or RB 120, might prove to be a beneficial treatment strategy for opioid drug addiction, though further studies are necessary.

Mitochondrial function in muscle from elderly athletes.

The extent to which mitochondria are involved in the aging process is controversial; much of the reported decline in mitochondrial oxidations in human skeletal muscle may be due to disease and inactivity rather than age. To study true aging, mitochondrial respiratory chain function was studied in 9 young and 12 elderly athletes. No significant deterioration with age was observed. If mitochondria are involved in aging, it must be through a more subtle mechanism than a global decline in respiratory chain activity.

Oligospermia and its relation with hormonal profile.

Serum of 161 oligospermic men was analysed for pituitary hormones LH and FSH and the androgen testosterone. The hormonal analysis indicated normal levels of LH and testosterone, while the FSH levels showed negative correlation to the sperm concentration.