Resolvin D1 Ameliorates Nicotinamide-streptozotocin-induced Type 2 Diabetes Mellitus by its Anti-inflammatory Action and Modulating PI3K/Akt/mTOR Pathway in the Brain.

OBJECTIVE: To study whether resolvin D1 (RvD1), a metabolite of docosahexaenoic acid (DHA), prevents NA-STZ-induced type 2 diabetes mellitus (type 2 DM) in vivo and if so, what could be the mechanism of this action. MATERIAL AND METHODS: Single intra-peritoneal (i.p) injection of NA-STZ (175 mg/kg body weight of NA and 65 mg/kg of STZ) was injected simultaneously with RvD1 (60 ng/animal) (injected for 5 consecutive days) to Wistar rats. The effect of RvD1 on plasma glucose levels and apoptotic (Bcl2/Bax) and inflammatory (NF-κB/iNOS) protein expression, plasma lipoxin A4 and BDNF (brain-derived neurotrophic factor) were studied. Protein expressions of PI3k-Akt-mTOR pathway along with histopathological studies of brain were also evaluated. RESULTS: NA-STZ-induced type 2 DM rats showed hyperglycemia, enhanced plasma IL-6/TNF-α (p ≤0.01), reduced plasma BDNF (p ≤0.01) and LXA4 (p ≤0.01) levels and low BDNF in pancreatic, hepatic and brain tissues (p <0.001), which were restored to near normal (p ≤0.01) in RvD1 treated group. RvD1 increased insulin sensitivity by suppressing inflammation (NF-κB/iNOS) (p ≤0.01) and decreasing apoptosis (Bcl2/Bax) and restoring BDNF and LXA4 levels to near normal. RvD1 treatment increased phosphorylation of Akt (Ser473), and subsequent activation (phosphorylation) of downstream signaling molecules of PI3K and mTOR indicating that RvD1 acts through PI3K/Akt/mTOR axis. DISCUSSION: RvD1 is effective in preventing NA-STZ-induced type 2 DM in vivo by suppressing oxidative damage, enhancing the production of anti-inflammatory LXA4 and enhancing neuronal cell survival by augmenting the production of BDNF. Thus, RvD1 may be of benefit not only in preventing diabetes mellitus but also diabetes associated Alzheimer's disease and memory loss.

Arachidonic acid-rich ARASCO oil has anti-inflammatory and antidiabetic actions against streptozotocin + high fat diet induced diabetes mellitus in Wistar rats.

OBJECTIVES: The aim of this study was to investigate the effects of arachidonic acid (AA)-rich ARASCO oil on high-fat diet (HFD) + streptozotocin (STZ)-induced diabetes mellitus in male Wistar rats and its possible mechanisms of action. METHODS: Male Wistar rats with HFD + STZ-induced diabetes were employed in the present study. ARASCO oil was administered orally for the first 7 d consecutively, followed by once weekly throughout the study (14 wk). At various time points, blood glucose and body weight and oral glucose tolerance tests were measured. At the end of the study, animals were sacrificed to collect plasma and various organs and stored at -80°C. Plasma insulin, tumor necrosis factor-α, interleukin-6, and lipoxin A4 were measured. Expression of the following genes was determined: nuclear factor-κΒ (NF-κB), cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LOX) in pancreas and lipocalin 2 (LPCLN2) in adipose tissue. Various antioxidants were measured in the plasma and other tissues. Area under the curve and insulin sensitivity index were assessed by computing homeostatic model of assessment for insulin resistance, quantitative insulin check index, Matsuda, and Belfiore indices. RESULTS: ARASCO oil treatment decreased hyperglycemia, restored insulin sensitivity, suppressed inflammation, enhanced plasma lipoxin A4 levels, and reversed altered antioxidant status to near normal in animals with HFD + STZ-induced diabetes. CONCLUSION: These results suggest that ARASCO, a rich source of AA, can prevent HFD + STZ-induced diabetes in Wistar rats owing to its anti-inflammatory action. It remains to be seen whether ARASCO oil is useful in preventing or postponing the development of type 2 diabetes mellitus in humans.

P300 and Heart Rate Variability Recorded Simultaneously in Meditation.

Sympathetic activation is required for attention. Separate studies have shown that meditation ( a) improves attention and ( b) reduces sympathetic activity. The present study assessed attention with the P300 and sympathetic activity with heart rate variability (HRV). Forty-seven male subjects (group mean age ± SD, 21.6 ± 3.4 years) were assessed in 4 mental states: ( a) random thinking, ( b) nonmeditative focusing, ( c) meditative focusing, and ( d) defocused meditation. These were recorded on 4 consecutive days. HRV, respiration, and P300 event-related potentials (ERPs) were recorded before and after the sessions. Data were analyzed with repeated-measures analysis of variance followed by post hoc analysis. HRV showed a significant increase in low-frequency (LF) power, decrease in high-frequency (HF) power and an increase in average heart rate based on the average R-R interval after meditative focusing, compared with before. In contrast, the average heart rate decreased after defocused meditation compared with before. There was a significant increase in the P300 peak amplitude after meditative focusing and defocused meditation, with a reduction in peak latency after defocused meditation. These results suggest that after meditation with focusing, there was sympathetic arousal whereas after defocused meditation, there was a decrease in the average heart rate while participants carried out the P300 auditory oddball task sooner.

Amelioration of streptozotocin-induced type 2 diabetes mellitus in Wistar rats by arachidonic acid.

Traditionally arachidonic acid (AA, 20:4 n-6) is considered as a pro-inflammatory molecule since it forms precursor to prostaglandins (PGs), leukotrienes (LTs) and thromboxanes (TXs) that have pro-inflammatory actions. Type 2 diabetes mellitus (type 2 DM) is considered as a low-grade systemic inflammatory condition in which circulating PGs and LTs are increased. Streptozotocin (STZ)-induced type 2 DM is used as a model of human type 2 DM in which peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and hyperglycemia occurs. In the present study, we observed that oral supplementation of AA prevented STZ-induced type 2 DM in Wistar rats by restoring hyperglycemia, plasma levels of TNF-α and IL-6; adipose tissue NF-kB and lipocalin 2 (LPCLN2) and pancreatic tissue NF-kB and 5- and 12- lipoxygenase enzymes to normal. AA treatment enhanced insulin sensitivity and plasma lipoxin A4 (LXA4) levels, a potent anti-inflammatory molecule derived from AA. These results are supported by our previous studies wherein it was noted that plasma phospholipid content of AA and circulating LXA4 levels are low in those with type 2 DM. In a preliminary study, we also noted that high-fat-diet (HFD)-induced type 2 DM in Wistar rats can be prevented by oral supplementation of AA. These results suggest AA has anti-inflammatory and anti-diabetic actions by enhancing the production of its anti-inflammatory metabolite LXA4.

Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo.

OBJECTIVE: The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action. METHODS: RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats. RESULTS: Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the pancreas and plasma TNF-α levels in T1- and T2DM; Nrf2, Glut2, COX2, and iNOS proteins in pancreatic tissue of T1DM and LPCLN2, NF-κb, IKB I in adipose tissue of T2DM reverted to normal in LXA4-treated animals. CONCLUSION: Both AA and LXA4 prevented STZ-induced cytotoxicity to RIN5 F cells in vitro and T1- and T2DM in vivo, suggesting that these two bioactive lipids may function as antidiabetic molecules. AA is beneficial against STZ-induced cytotoxicity and T1- and T2DM by enhancing the production of LXA4.

Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.

OBJECTIVE: We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. MATERIAL AND METHODS: In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-α and antioxidants, lipid peroxides and nitric oxide were measured. RESULTS: Of all, arachidonic acid (AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. DISCUSSION: AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017.

Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.

In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs) tested on human neuroblastoma IMR-32 (0.5 × 10(4) cells/100 µl of IMR) cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively) at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2) and leukotrienes (LTD4 and LTE4) tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4), 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA) and 10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S),17(S)DiHDoHE), metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA) at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

The effect of yoga on neuroticism in an Indian population varies with socio-demographic factors.

Neuroticism, or negative affectivity, can influence a person's approach to life. This study examined levels of neuroticism in 249 patients with illnesses known to be related to the mental state. All of them were given a six-day intensive yoga program. Patients showed a decrease in neuroticism measured by the PGI Health Questionnaire. The reduction was maximum for (a) those with ages between 36 and 51 years, (b) females, (c) patients with at least 17 years of education, and (d) those who were self-employed. The results show the importance of socio-demographic factors in neuroticism levels and in programs intended to reduce neuroticism. Hence, yoga is a useful intervention to reduce traits of neuroticism, with variations in the degree of change based on social factors.

Meditation and attention: a comment on a recent article.

Meditation and attention are considered associated in different ways. For example, contemporary concepts state that to meditate, a practitioner has either to (i) focus attention on the object of meditation (FA) or (ii) maintain vigilance and disengage their attention consciously from all distracters (OM). The Indian sage Patanjali (circa 900 B.C.), mentioned that there are two stages of meditation, which differ subtly from the descriptions of FA and OM. One stage is called dharana, or focusing attention on the object of meditation. Another stage is called dhyana, during which all thoughts remain effortlessly directed to the object of meditation, excluding all other thoughts. Vigilance and attention are not required during dhyana, which is the actual phase of meditation. In a previous study, participants who practiced dharana performed better in a task for selective attention than those who practiced dhyana. Brainstem auditory evoked potential changes during the two states differed. Descriptions of yoga practices from ancient texts can give added insights about meditation and attention, supported by objective assessments.

Effect of yoga on musculoskeletal discomfort and motor functions in professional computer users.

The self-rated musculoskeletal discomfort, hand grip strength, tapping speed, and low back and hamstring flexibility (based on a sit and reach task) were assessed in 291 professional computer users. They were then randomized as Yoga (YG; n=146) and Wait-list control (WL; n=145) groups. Follow-up assessments for both groups were after 60 days during which the YG group practiced yoga for 60 minutes daily, for 5 days in a week. The WL group spent the same time in their usual recreational activities. At the end of 60 days, the YG group (n=62) showed a significant decrease in the frequency, intensity and degree of interference due to musculoskeletal discomfort, an increase in bilateral hand grip strength, the right hand tapping speed, and low back and hamstring flexibility (repeated measures ANOVA and post hoc analysis with Bonferroni adjustment). In contrast, the WL group (n=56) showed an increase in musculoskeletal discomfort and a decrease in left hand tapping speed. The results suggest that yoga practice is a useful addition to the routine of professional computer users.

Yoga reduces symptoms of distress in tsunami survivors in the andaman islands.

A month after the December 2004 tsunami the effect of a 1 week yoga program was evaluated on self rated fear, anxiety, sadness and disturbed sleep in 47 survivors in the Andaman Islands. Polygraph recordings of the heart rate, breath rate and skin resistance were also made. Among the 47 people, 31 were settlers from the mainland (i.e. India, ML group) and 16 were endogenous people (EP group). There was a significant decrease in self rated fear, anxiety, sadness and disturbed sleep in both groups, and in the heart and breath rate in the ML group, and in the breath rate alone in the EP group, following yoga (P < 0.05, t-test). This suggests that yoga practice may be useful in the management of stress following a natural disaster in people with widely differing social, cultural and spiritual beliefs.

Effect of yoga on self-rated visual discomfort in computer users.

BACKGROUND: 'Dry eye' appears to be the main contributor to the symptoms of computer vision syndrome. Regular breaks and the use of artificial tears or certain eye drops are some of the options to reduce visual discomfort. A combination of yoga practices have been shown to reduce visual strain in persons with progressive myopia. The present randomized controlled trial was planned to evaluate the effect of a combination of yoga practices on self-rated symptoms of visual discomfort in professional computer users in Bangalore. METHODS: Two hundred and ninety one professional computer users were randomly assigned to two groups, yoga (YG, n = 146) and wait list control (WL, n = 145). Both groups were assessed at baseline and after sixty days for self-rated visual discomfort using a standard questionnaire. During these 60 days the YG group practiced an hour of yoga daily for five days in a week and the WL group did their usual recreational activities also for an hour daily for the same duration. At 60 days there were 62 in the YG group and 55 in the WL group. RESULTS: While the scores for visual discomfort of both groups were comparable at baseline, after 60 days there was a significantly decreased score in the YG group, whereas the WL group showed significantly increased scores. CONCLUSION: The results suggest that the yoga practice appeared to reduce visual discomfort, while the group who had no yoga intervention (WL) showed an increase in discomfort at the end of sixty days.

Changes in middle latency auditory evoked potentials during meditation.

In the present study of middle latency auditory evoked potentials during Brahmakumaris Raja Yoga meditation there was a decrease in the peak latency of the Na wave (a negative wave between 14 and 19 msec.) during meditation. Since the neural generator of this wave lies at the midbrain-thalamic level, from the results one can infer that the meditation reduces conduction time at this level.

An evaluation of the ability to voluntarily reduce the heart rate after a month of yoga practice.

The study aimed at determining whether novices to yoga would be able to reduce their heart rate voluntarily and whether the magnitude of reduction would be more after 30 days of yoga training. Two groups (yoga and control, n = 12 each) were assessed on Day 1 and on Day 30. During the intervening 30 days, the yoga group received training in yoga techniques while the control group carried on with their routine. At each assessment the baseline heart rate was recorded for one minute, this was followed by a six-minute period during which participants were asked to attempt to voluntarily reduce their heart rate, using any strategy. Both the baseline heart rate and the lowest heart rate achieved voluntarily during the six-minute period were significantly lower in the yoga group on Day 30 compared to Day 1 by a group average of 10.7 beats per minute (i.e., bpm) and 6.8 bpm, respectively (p < .05, Wilcoxon paired signed ranks test). In contrast, there was no significant change in either the baseline heart rate or the lowest heart rate achieved voluntarily in the control group on Day 30 compared to Day 1. The results suggest that yoga training can enable practitioners to use their own strategies to reduce the heart rate, which has possible therapeutic applications.

Sensory perception during sleep and meditation: common features and differences.

Sleep and meditation are both physiological conditions in which peripheral sensory input is voluntarily reduced, but sensory perception of internally generated information continues. However, the two conditions differ in the level of awareness retained.