Nanocarrier mediated drug delivery as an impeccable therapeutic approach against Alzheimer's disease.

For the past several years, dementia, is one of the predominantly observed groups of symptoms in a geriatric population. Alzheimer's disease (AD) is a progressive memory related neurodegenerative disease, for which the current Food and drug administration approved therapeutics are only meant for a symptomatic management rather than targeting the root cause of AD. These therapeutics belong to two classes, Acetylcholine Esterase inhibitors and N-methyl D-aspartate antagonist. Furthermore, to facilitate neuroprotective action in AD, the drugs are majorly expected to reach the specific target area in the brain for the desired efficacy. Thus, there is a huge requirement for drug discovery and development for facilitating the entry of drugs more in brain to exert a specific action. The very first line of defense and the major limitation for the entry of drugs into the brain is the Blood Brain Barrier, followed by Blood-Cerebrospinal Fluid Barrier. More than a barrier, these mainly act as selectively permeable membranes, which allows entry of specific molecules into the brain. Furthermore, specific enzymes result in the degradation of xenobiotics. All these mechanisms pose as hurdles in the way of effective drug delivery in the brain. Thus, novel techniques need to be harbored for the facilitation of the delivery of such drugs into the brain. Nanocarriers are advantageous for facilitating the specific targeted drug treatment in AD. As nanomedicines are one of the novels and most useful approaches for AD, thus the present review mainly focuses on understanding the advanced use of nanocarriers for targeted drug delivery in the management of AD.

In-line treatments and clinical initiatives to fight against COVID-19 outbreak.

In December 2019, when the whole world is waiting for Christmas and New Year, the physicians of Wuhan, China, are astounded by clusters of patients suffering from pneumonia from unknown causes. The pathogen isolated from the respiratory epithelium of the patients is similar to previously known coronaviruses with some distinct features. The disease was initially called nCoV-2019 or SARS-nCoV-2 and later termed as COVID-19 by WHO. The infection is rapidly propagating from the day of emergence, spread throughout the globe and now became a pandemic which challenged the competencies of developed nations in terms of health care management. As per WHO report, 216 countries are affected with SARS-CoV-19 by August 5, 2020 with 18, 142, 718 confirmed cases and 691,013 deaths reports. Such huge mortality and morbidity rates are truly threatening and calls for some aggressive and effective measures to slow down the disease transmission. The scientists are constantly engaged in finding a potential solution to diagnose and treat the pandemic. Various FDA approved drugs with the previous history of antiviral potency are repurposed for COVID-19 treatment. Different drugs and vaccines are under clinical trials and some rapid and effective diagnostic tools are also under development. In this review, we have highlighted the current epidemiology through infographics, disease transmission and progression, clinical features and diagnosis and possible therapeutic approaches for COVID-19. The article mainly focused on the development and possible application of various FDA approved drugs, including chloroquine, remdesivir, favipiravir, nefamostate mesylate, penciclovir, nitazoxanide, ribavirin etc., vaccines under development and various registered clinical trials exploring different therapeutic measures for the treatment of COVID-19. This information will definitely help the researchers to understand the in-line scientific progress by various clinical agencies and regulatory bodies against COVID-19.

Effect of Eurycoma longifolia standardised aqueous root extract-Physta® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study.

BACKGROUND: Low testosterone levels cause physiological changes that compromise the quality of life in ageing men. A standardised water extract from the root of Eurycoma longifolia (EL), known as Physta®, is known to increase testosterone levels. OBJECTIVE: To evaluate the safety and efficacy of Physta® in improving the testosterone levels and quality of life in ageing male subjects. DESIGN: This randomised, double-blind, placebo-controlled study enrolled 105 male subjects aged 50-70 years with a testosterone level <300 ng/dL, BMI ≥ 18 and ≤30.0 kg/m2. The subjects were given either Physta® 100 mg, 200 mg or placebo daily for 12 weeks. The primary endpoints were changes in serum total and free testosterone levels. The secondary endpoints included changes in the level of sex hormone-binding globulin (SHBG), dihydroepiandrosterone (DHEA), glycated haemoglobin (HbA1c), insulin-like growth factor-1 (IGF-1), thyroid function tests (T3, T4, TSH and Free T3) and cortisol. Changes in Ageing Male Symptoms (AMS) score, Fatigue Severity Scale (FSS) score and muscle strength are other secondary endpoints. The safety of the intervention products was measured by complete blood count, lipid profile, liver and renal function tests. RESULTS: There was a significant increase in the total testosterone levels at week 12 (P < 0.05) in the Physta® 100 mg group and at weeks 4 (P < 0.05), 8 (P < 0.01) and 12 (P < 0.001) in the Physta® 200 mg group compared to placebo. No significant between-group differences in free testosterone levels were observed but a significant within-group increase occurred at weeks 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta®100 mg group and at weeks 2 (P < 0.01), 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta® 200 mg group. The AMS and FSS showed significant reduction (P < 0.001) in total scores at all time-points within- and between-group in both Physta® groups. DHEA levels significantly increased (P < 0.05) within-group in both Physta® groups from week 2 onwards. Cortisol levels significantly (P < 0.01) decreased in the Physta® 200 mg group, while muscle strength significantly (P < 0.001) increased in both Physta® groups at week 12 in the within-group comparison. There were no significant changes in SHBG. No safety related clinically relevant changes were observed. CONCLUSION: Supplementation of Physta® at 200 mg was able to increase the serum total testosterone, reduce fatigue and improve the quality of life in ageing men within 2 weeks' time. TRIAL REGISTRATION: This clinical study has been registered in ctri.nic.in (CTRI/2019/03/017959).

Effect of herbal extract Eurycoma longifolia (Physta®) on female reproductive hormones and bone biochemical markers: an ovariectomised rat model study.

BACKGROUND: Each year 1.5 million women experience menopause when menstrual cycles cease resulting from the loss of ovarian function and oestrogen deprivation, a hormone that helps prevent bone loss. This study investigated the effects of Physta®, a standardized herbal extract of Eurycoma longifolia Jack (PEL), on hormonal balance and parameters associated with hormonal imbalance, namely body and uterus weight and bone biochemical markers relevant in menopausal symptoms. METHODS: Forty-eight Sprague Dawley rats were randomly divided into six groups of eight rats each: (A) Sham operated; control (B) Untreated (ovariectomised (OVX) with vehicle), (C) PEL 100 (OVX + 100 mg/kg body weight (bw)), (D) PEL 300 (OVX + 300 mg/kg bw), (E) PEL 500 (OVX + 500 mg/kg bw) and (F) Positive control, testosterone undecanoate (TU) (OVX+ 10 mg/kg bw). Group A and B received daily oral administrations of the vehicle, Group C-E received daily oral administration of PEL and Group F received testosterone undecanoate intramuscularly weekly. At the end of 8 weeks, serum calcium, phosphate, bone alkaline phosphatase (BALP), osteocalcin, follicle stimulating hormone (FSH), luteinising hormone (LH), oestrogen, progesterone and testosterone were measured, then the animals were sacrificed and uterus was isolated, while weight was recorded in all experimental groups. RESULTS: Treatment of OVX rats with PEL at a dose of 500 mg/kg showed decreased serum FSH (P < 0.001, 4.25 ± 0.22 mIU/ml) and LH (NS, 4.07 ± 0.12 mIU/ml), while there was a significant increase in progesterone (P < 0.05, 2.48 ± 0.08 ng/ml) and oestrogen (P < 0.05, 11.02 ± 0.13 pg/ml) levels when compared to untreated group. PEL treatment at doses of 100 mg/kg, 300 mg/kg and 500 mg/kg showed a non-significant but increasing trend in serum calcium, phosphate, bone alkaline phosphate and testosterone levels. Ovariectomy resulted in a significant reduction (P < 0.001, 238.81 ± 5.39 mg) in uterus weight in the ovariectomised rats, which was alleviated in all PEL treated ovariectomised rats with an increasing trend of uterine weight. CONCLUSION: The results suggest that PEL could be protective and beneficial for the management of reproductive hormone and bone markers. Therefore, it could be used to address hormonal imbalances and symptoms associated with menopause.

Effects of a Proprietary Standardized Orthosiphon stamineus Ethanolic Leaf Extract on Enhancing Memory in Sprague Dawley Rats Possibly via Blockade of Adenosine A 2A Receptors.

The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo, possibly via blockade of adenosine A2A receptors (A2AR). The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74% inhibition at 150 µg/ml and significant A2AR antagonist activity with 98% inhibition at 300 µg/mL. A significant adenosine A1 receptor (A1R) antagonist activity with 100% inhibition was observed at 300 µg/mL. Its effect on learning and memory was assessed via social recognition task using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant (p < 0.001) change in recognition index (RI) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p., respectively, compared to the vehicle control. In comparison, the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion; however, it remained insignificant in RI at 200 mg/kg p.o. Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory and the possible involvement of adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory.

Anti-inflammatory effects of Polygonum minus (Huds) extract (Lineminus™) in in-vitro enzyme assays and carrageenan induced paw edema.

BACKGROUND: The study was aimed to evaluate the anti-inflammatory activity of ethanolic and aqueous extracts of Polygonum minus (Huds) using in vitro and in vivo approaches. METHODS: The in vitro tests used to evaluate ethanolic extract are cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), lipooxygenase (5-LOX), secretory phospholipase-A2 (sPLA2) inhibition assay whilst the in-vivo effect was measured by the ability of aqueous extracts to reduce paw edema induced by λ-carrageenan, in rats. RESULTS: The ethanolic extract inhibited the activities of 5-LOX and COX-1(p < 0.05) whilst the inhibitory effect on COX-2 was only moderate. A marked inhibition of 5-LOX was observed at 30 µg/ ml. The extract did not inhibit the activity of sPLA2. The ability of the ethanolic extracts of Polygonum minus to inhibit both 5-LOX and COX, prompted a study to evaluate the effects of using an aqueous extract of Polygonum minus(LineminusTM); as this would be more suitable for future clinical testing. The anti-inhibitory activity of the aqueous extract from this plant was evaluated using a rat model where inflammation was induced in the paws by injection of λ-carrageenan. The aqueous extracts from Polygonum minus administered at doses of 100 and 300 mg/kg body weight (b.w.), significantly (p < 0.01) reduced paw edema induced by λ-carrageenan in the experimental model, at 4 h compared to the vehicle control. Furthermore, administration of 100 mg/kg b.w. or 300 mg/kg b.w. completely reduced inflammation of the paw 4 h after injection. CONCLUSION: These findings suggest that aqueous extract of Polygonum minus possesses potent anti-inflammatory activities.