Emodin (from
Cascara sagrada) is antiproliferative [
link to www.pubfacts.com] [
link to www.pubfacts.com] - a property dependent on its ability to inhibit the signaling of a group of CREB-supporting kinases (MAPK) that play a part in typical diabetic issues.
At 2 months of diabetes, insulin-deficient diabetic control rats exhibited significant increases in retinal superoxide, nitric oxide (NO), cyclooxygenase (COX)-2, and leukostasis within retinal microvessels. All these abnormalities were significantly inhibited by the p38 MAPK inhibitor (25 mg/kgBW/d). At 10 months of diabetes, significant increases in the number of degenerate (acellular) capillaries and pericyte ghosts were measured in control diabetic rats versus those in nondiabetic control animals, and pharmacologic inhibition of p38 MAPK significantly inhibited all these abnormalities (all P < 0.05). This therapy also had beneficial effects outside the eye in diabetes, as evidenced by the inhibition of a diabetes-induced hypersensitivity of peripheral nerves to light touch (tactile allodynia).
Quoting: [link to www.ncbi.nlm.nih.gov] Apparently emodin is able to achieve this by increasing expression of the PPARG gene. [
link to www.pubfacts.com]
Emodin also antagonizes the P2X7 (a purinergic) receptor. [
link to www.ncbi.nlm.nih.gov]
This antipurinergic property is shared by sumarin, a drug hinted at in the OP that could benefit ASD by restabilizing metabolic function.
Berberine (from the bark of phellodendron) also ameliorates overactivation of the p38 MAPK pathway (thus reducing phospho-CREB) [
link to www.pubfacts.com] and is antidiabetic/prometabolic.
RESULTS: After berberine administration, patients had a remission of 36% (P=0.037) in the presence of metabolic syndrome and a significant decrease in waist circumference in females (106±4 vs. 103±3 cm, P<0.05), systolic blood pressure (SBP) (123±7 vs. 115±9 mmHg, P<0.01), triglycerides (2.4±0.7 vs. 1.4±0.5 mmol/L, P<0.01), area under the curve (AUC) of glucose (1182.1±253.6 vs. 1069.5±172.4 mmol/l, P<0.05), AUC of insulin (92,056±72,148 vs. 67,407±46,441 pmol/L, P<0.01), and insulinogenic index (0.78±0.69 vs. 0.62±0.46, P<0.05), as well as an increase in the Matsuda index (2.1±1.0 vs. 3.1±1.6, P<0.01).
CONCLUSIONS: Administration of berberine leads to remission of metabolic syndrome and decreases in waist circumference, SBP, triglycerides, and total insulin secretion, with an increase in insulin sensitivity.
Quoting: [link to www.ncbi.nlm.nih.gov] To suppress NO formation & CREB activation, the mitigation of oxidative stress is crucial.
Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway. [
link to www.pubfacts.com]
Retinoic acid (metabolite of vitamin A) also has this ability [
link to www.pubfacts.com] and is crucial for D2R mRNA expression. [
link to www.ncbi.nlm.nih.gov]
More on AGEs: [
link to blog.cholesterol-and-health.com]
The dysregulation of blood glucose has a key role in sustaining these vicious circles by relentlessly keeping CREB activated, perpetuating the numbness that would seek remediation through overeating & the like. Suppressing CREB is of obvious desirability.
A thirst to allay thirst.
