186
S. D. Shnyder and C. W. Wright
6 Antidiabetic Activity
In an earlier work by Bierer et al. in 1998 [22, 23], as reviewed in [1], it was reported
that extracts of C. sanguinolenta and cryptolepine (1) have hypoglycemic effects
in genetically altered obese mice [22]. In addition, 1 stimulated glucose transport
in 3T3-L1 adipocytes and was active in a non-insulin-dependent rat diabetes model
[23]. The 4-methoxy- and N-5 benzyl-analogs of 1 were also found to reduce glucose
levels in diabetic animal models. More recently, 1 (10–30 mg/kg orally) was shown
to reduce fasting blood glucose and body weight in alloxan-induced diabetic rats and
reduced some complications of diabetes including neuropathic pain, hyperlipidemia,
and pancreatic β-cell islet damage but did not improve liver and kidney damage or
reduce semen quality [24]. These studies lend some support to traditional use of C.
sanguinolenta in the treatment of diabetes.
7 Anti-inflammatory Activity
Cryptolepis sanguinolenta is used traditionally for the treatment of inflammatory
disorders and, in support of this, the methanolic extract of the roots as well as
purified 1 have been shown to have anti-inflammatory activities [25]. In a study
exploring its anti-inflammatory mechanism of action, it was found that lipopolysaccharide (LPS)-induced nitric oxide production in murine RAW 264.7 macrophage
cells was inhibited dose-dependently by 1 at concentrations of 2.5–10 μM and that
the action of transcription factor nuclear factor-κB (NF-κB) was strongly inhibited
due to reduced binding to DNA and decreased transcription of NF-κB-regulated
proinflammatory proteins [25]. Further support for the anti-inflammatory activity of
1 is the demonstration of in vivo anti-inflammatory activity in animal models [26].
Carrageenan-induced rat paw edema and pleurisy were dose-dependently inhibited
by 10–40 mg/kg of 1 given intraperitoneally. LPS-induced microvascular permeability and acetic acid-induced writhing were similarly inhibited but oral doses of 40
mg/kg for four days did not induce gastric lesion formation [26].
The dried methanol extract of C. sanguinolenta roots as well as 1 inhibited
inflammation in interleukin (IL)-1β-induced SK-N-SH neuroblastoma cells and 1
significantly and dose-dependently inhibited TNF-α, IL-6 and prostaglandin (PG) E 2
production without affecting cell viability [27]. An investigation of the underlying
mechanism revealed that NF-κBp65 nuclear translocation and phosphorylation of
p38 mitogen-activated protein kinase (MAPK) were inhibited. Pre-treatment of the
cells with 1 (10 and 20 μM) inhibited IL-1β-induced gene and protein expressions of
cyclooxygenase 2 (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1).
In a related study, 1 was shown to inhibit neuroinflammation in LPS-activated rat
microglia, and the mechanisms involved were similar to those found with SK-N-SH
cells [28].
S. D. Shnyder and C. W. Wright
6 Antidiabetic Activity
In an earlier work by Bierer et al. in 1998 [22, 23], as reviewed in [1], it was reported
that extracts of C. sanguinolenta and cryptolepine (1) have hypoglycemic effects
in genetically altered obese mice [22]. In addition, 1 stimulated glucose transport
in 3T3-L1 adipocytes and was active in a non-insulin-dependent rat diabetes model
[23]. The 4-methoxy- and N-5 benzyl-analogs of 1 were also found to reduce glucose
levels in diabetic animal models. More recently, 1 (10–30 mg/kg orally) was shown
to reduce fasting blood glucose and body weight in alloxan-induced diabetic rats and
reduced some complications of diabetes including neuropathic pain, hyperlipidemia,
and pancreatic β-cell islet damage but did not improve liver and kidney damage or
reduce semen quality [24]. These studies lend some support to traditional use of C.
sanguinolenta in the treatment of diabetes.
7 Anti-inflammatory Activity
Cryptolepis sanguinolenta is used traditionally for the treatment of inflammatory
disorders and, in support of this, the methanolic extract of the roots as well as
purified 1 have been shown to have anti-inflammatory activities [25]. In a study
exploring its anti-inflammatory mechanism of action, it was found that lipopolysaccharide (LPS)-induced nitric oxide production in murine RAW 264.7 macrophage
cells was inhibited dose-dependently by 1 at concentrations of 2.5–10 μM and that
the action of transcription factor nuclear factor-κB (NF-κB) was strongly inhibited
due to reduced binding to DNA and decreased transcription of NF-κB-regulated
proinflammatory proteins [25]. Further support for the anti-inflammatory activity of
1 is the demonstration of in vivo anti-inflammatory activity in animal models [26].
Carrageenan-induced rat paw edema and pleurisy were dose-dependently inhibited
by 10–40 mg/kg of 1 given intraperitoneally. LPS-induced microvascular permeability and acetic acid-induced writhing were similarly inhibited but oral doses of 40
mg/kg for four days did not induce gastric lesion formation [26].
The dried methanol extract of C. sanguinolenta roots as well as 1 inhibited
inflammation in interleukin (IL)-1β-induced SK-N-SH neuroblastoma cells and 1
significantly and dose-dependently inhibited TNF-α, IL-6 and prostaglandin (PG) E 2
production without affecting cell viability [27]. An investigation of the underlying
mechanism revealed that NF-κBp65 nuclear translocation and phosphorylation of
p38 mitogen-activated protein kinase (MAPK) were inhibited. Pre-treatment of the
cells with 1 (10 and 20 μM) inhibited IL-1β-induced gene and protein expressions of
cyclooxygenase 2 (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1).
In a related study, 1 was shown to inhibit neuroinflammation in LPS-activated rat
microglia, and the mechanisms involved were similar to those found with SK-N-SH
cells [28].