An extract from a
PDB static culture of Malbranchea
dendritica exhibited α-glucosidase and PTP-1B
inhibitory activities. Fractionation of the active extract led to
the isolation of gymnoascolide A (1), a γ-butenolide,
and xanthones sydowinin A (2), sydowinin B (3), and AGI-B4 (4), as well as orcinol (5). Compound 1 exhibited important inhibitory activity
against yeast α-glucosidase (IC50 = 0.556 ±
0.009 mM) in comparison to acarbose (IC50 = 0.403 ±
0.010 mM). Kinetic analysis revealed that 1 is a mixed-type
inhibitor. Furthermore, compound 1 significantly reduced
the postprandial peak in mice during a sucrose tolerance test at the
doses of 5.16 and 10 mg/kg. Compound 1 was reduced with
Pd/C to yield a mixture of enantiomers 1a and 1b; the mixture showed similar activity against α-glucosidase
(IC50 = 0.396 ± 0.003 mM) and kinetic behavior as
the parent compound but might possess better drug-likeness properties
according to SwissADME and Osiris Property Explorer tools. Docking
analysis with yeast α-glucosidase (pdb: 3A4A) and the C-terminal
subunit of human maltase-glucoamylase (pdb: 3TOP) predicted that 1, 1a, and 1b bind to an allosteric
site of the enzymes. Compounds 1–5 were evaluated against PTP-1B, but only xanthone 3 moderately
inhibited in a noncompetitive fashion the enzyme with an IC50 of 0.081 ± 0.004 mM. This result was consistent with that of
docking analysis, which revealed that 3 might bind to
an allosteric site of the enzyme. From the inactive barley-based semisolid
culture of M. dendritica, the natural
pigment erythroglaucin (6) and the nucleosides deoxyadenosine
(7), adenosine (8), thymidine (9), and uridine (10) were also isolated and identified.
The roots of the
cactus
Peniocereus greggii
, which
grows in Northern Mexico and in the south of Arizona, are highly valued
by the Pima to treat diabetes and other illnesses, such as breast
pain and common cold. As part of our chemical and pharmacological
investigation on medicinal plants used for treating diabetes, herein
we report the hypoglycemic and antihyperglycemic action of a decoction
prepared from the roots of the plant. The active compounds were a
series of cholestane steroids, namely, peniocerol (
2
),
desoxyviperidone (
3
), viperidone (
4
), and
viperidinone (
5
). Also, a new chemical entity was obtained
from an alkalinized chloroform extract (CE1), which was characterized
as 3,6-dihydroxycholesta-5,8(9),14-trien-7-one (
6
) by
spectroscopic means. Desoxyviperidone (
3
) showed an antihyperglycemic
action during an oral glucose tolerance test. Compound
3
was also able to decrease blood glucose levels during an intraperitoneal
insulin tolerance test in hyperglycemic mice only in combination with
insulin, thus behaving as an insulin sensitizer agent. Nevertheless,
mitochondrial bioenergetic experiments revealed that compounds
3
and
6
increased basal respiration and proton
leak, without affecting the respiration associated with ATP production
in C2C12 myotubes. Finally, an ultraefficiency liquid chromatographic
method for quantifying desoxyviperidone (
3
) and viperidone
(
4
) in the crude drug was developed and validated. Altogether,
our results demonstrate that
Peniocereus greggii
decoction
possesses a hypoglycemic and antihyperglycemic action in vivo, that
sterols
2
and
6
promotes insulin secretion
in vitro, and that desoxyviperidone (
3
) physiologically
behaves as an insulin sensitizer agent by a mechanism that may involve
mitochondrial proton leak.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.