Antihyperglycemic activity with DPP-IV inhibition of alkaloids from seed extract of Castanospermum australe: Investigation by experimental validation and molecular docking.
The antidiabetic actions of Castanospermum australe Cunn., seed (CAS) extract were evaluated in Poloxamer-407 (PX-407) induced T2DM rats. The CAS extract (100 and 150 mg/kg body weight) was administered orally once a day for 5 weeks after the animals were confirmed diabetic. A significant increase in blood glucose, HbA₁c and serum insulin levels were observed in T2DM rats in comparison to citrate control rats. Treatment with CAS extract in T2DM rats reduced the elevated levels of blood glucose, HbA₁c and insulin with significant (p≤0.001) improvement in OGT. The CAS extract treatment also increased (p≤0.001) the K(ITT) and prevented increase in HOMA-R level in T2DM rats. The DPP-IV inhibitory potential of CAS extract showed IC₅₀ value of 13.96 μg/ml whilst the standard Diprotin A displayed the IC₅₀ value of 1.543 μg/ml. Molecular docking of the three reported alkaloids from the seeds of C. australe showed comparable DPP-IV inhibition with berberine. Our data suggest that CAS extract (150 mg/kg body weight) normalizes hyperglycemia in T2DM rats with strong DPP-IV inhibitory potential. The molecular docking showed that among the three alkaloids of seed extract 7-Deoxy-6-epi-castanospermine is a potent DPP-IV inhibitor similar to berberine.
Department of Biochemistry, Patna University, Patna 800005, Bihar, India. sudhanshu_bharti@rediffmail.com
Sudhanshu Kumar
SK
Bharti
Supriya
S
Krishnan
Amit
A
Kumar
Kaushal Kishore
KK
Rajak
Krishna
K
Murari
Binod Kumar
BK
Bharti
Ashok Kumar
AK
Gupta
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001599:Berberine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D031291:Castanospermum / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007212:Indolizines / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D062105:Molecular Docking Simulation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020442:Poloxamer; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds
D000470:Alkaloids; D001599:Berberine; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007212:Indolizines; D007328:Insulin; D010936:Plant Extracts; D020442:Poloxamer; C065752:7-deoxycastanospermine