Background
Abrus precatorius
possesses various therapeutic properties including anticancer potentials. This study evaluated the anti-proliferative activities of fractions of methanol root extract of
...A. precatorius
on breast and cervical cancer cells and their immunomodulatory effect. Phytochemical screening was done by FTIR and GCMS. In vitro anti-proliferative effect was evaluated on human breast cancer (AU565) and cervical cancer (HeLa) cells and on murine fibroblast (NIH 3 T3) cells. Antioxidant activity was performed via DPPH radical scavenging assay. The immunomodulatory potential of fractions was evaluated by inhibition of phagocytes oxidative burst (ROS), Nitric oxide (NO) and proinflammatory cytokine TNF-α.
Results
A. precatorius
fractions showed different chemical groups and were somewhat selective in antiproliferative activity against studied cancer cells. Ethyl acetate fraction showed the most significant antiproliferative activity with IC
50
values of 18.10 μg/mL and 11.89 μg/mL against AU565 and HeLa cells respectively. Hexane fraction significantly (
p
< 0.05) inhibited HeLa cells (IC
50
18.24 ± 0.16 μg/mL), whereas aqueous fraction showed mild inhibition (IC
50
46.46 ± 0.14 μg/mL) on AU565 cell proliferation. All fractions showed no cytotoxicity against NIH-3 T3 murine fibroblast normal cells. All fractions showed potent and significant (
p
< 0.001) DPPH radical scavenging activity as well as suppressed phagocytic oxidative burst. Hexane (< 1 μg/mL), ethyl acetate (< 1 μg/mL), and butanol (5.74 μg/mL) fractions potently inhibited the cytokine TNF- α, hexane (< 1 μg/mL) and ethyl acetate (< 1 μg/mL) fractions also potently inhibited NO.
Conclusions
The antiproliferative activities and suppressive effect on the phagocytic oxidative burst, NO and proinflammatory cytokine might be due to the synergistic actions of bioactive compounds especially flavonoids present in the assayed fractions and therefore, suggest chemotherapeutic use of
A. precatorius
in cancer treatment.
Doxorubicin (DOX) is an anthracyclin antibiotic used for the treatment of various cancers. Nephrotoxicity is among the serious side effects of DOX, therefore, DOX-induced nephrotoxic model has been ...widely used to study nephropathies. The objectives of this study is to investigate the possible anti-inflammatory and nephroprotective effects of salicylic acid derivative, N-(2-hydroxy phenyl) acetamide (NA-2), in a rat model of DOX-induced nephrotoxicity. The in vitro anti-inflammatory potential of NA-2 was manifested by whole blood oxidative burst and nitric oxide (NO) assays with no toxicity on normal human fibroblast (BJ) cells, human embryonic kidney (HEK-293) cells, and normal monkey kidney epithelial (Vero) cells. The in vivo study included five groups: Normal control, DOX (6 mg/kg DOX-i.v.via tail vein), NA-2 treated control-i.p., NA-2/DOX treated-i.p., and prednisolone/DOX treated. After 7 days of DOX administration, rats with urinary protein level of >50 mg/kg/day were selected. Treatment group rats received i.p. doses of NA-2 (10 mg/kg/day) for 3 weeks with weekly monitoring of urinary protein excretion and body weights. mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and kidney injury molecule (KIM)-1 was analyzed by quantitative polymerase chain reaction (qPCR). Protein expressions were analyzed by immunohistochemistry. NA-2 attenuated DOX-induced changes in serum and urine levels, and improved inflammatory profile of the renal tissue. Histopathological findings revealed protective effects of NA-2 showing lesser lesions. We conclude that NA-2 is able to protect against DOX-induced renal damage functionally, biochemically and histopathologically with corresponding improvement in the kidney inflammatory profile.
Urease plays a major role in the pathogenesis of peptic and gastric ulcer and also causes acute pyelonephritis and development of infection-induced reactive arthritis. Carbonic anhydrases (CA) cause ...pathological disorders such as epilepsy (CA I), glaucoma, gastritis, renal, pancreatic carcinomas, and malignant brain tumors (CA II). Although various synthetic urease and carbonic anhydrase inhibitors are known, these have many side effects. Hence, present studies were undertaken on ethyl acetate extract of
, an endophytic fungus separated from the leaves of
Linn. and led to the isolation of five furanoxanthones, sterigmatin (1: ), sterigmatocystin (3: ), dihydrosterigmatocystin (4: ), oxisterigmatocystin C (5: ), acyl-hemiacetal sterigmatocystin (6: ), and a pyranoxanthone (2: ). Acetylation of 3: gave compound
-acetyl sterigmatocystin (7: ). Their chemical structures were elucidated by
H and
C NMR and MS. The inhibitory effect of isolated compounds was evaluated on urease and carbonic anhydrase (
CA II) enzymes
Compounds 3: and 6: showed significant urease inhibition (IC
19 and 21 µM), while other compounds exhibited varying degrees of urease inhibition (IC
33 - 51 µM). Compounds 4, 6: and 7: exhibited significant inhibition of
CA II (IC
values 21, 25 and 18 µM respectively), compounds 1: -3: displayed moderate inhibition (IC
61, 76 and 31 µM respectively) while 5: showed no inhibition. A mechanistic study of the most active urease inhibitors was also performed using enzyme kinetics and molecular docking. All compounds were found non-toxic on the NIH-3T3 cell line.
The current study describes the preparation of nano-formulation of propyl gallate (NPG vesicles) comprised of soya bean extracted soya-lecithin. The compound was evaluated for its
in-vitro
and
...in-vivo
anti-oxidative and anti-inflammatory properties in addition with acute toxicity analysis in Wistar rats. Nano-carrier preparation acquired the film hydration method, while the evaluation for size distribution was carried out through dynamic light scattering (DLS) analysis. FTIR spectroscopy was used to identify the interaction between active material with excipient. Whereas, morphological evaluation was carried out by using atomic force microscopy (AFM). UV-visible spectrophotometer was used to measure the efficacy for drug encapsulation. The synthesized nano-carriers of propyl gallate has particle size of 201 ± 2.5 nm, with spherical morphology. The PDI index of nano-formulation is; 0.192 ± 0.8 indicates uniform size distribution with zeta potential − 43.4 ± 1.7mV values representing their highly stable nature. The drug encapsulation efficiency of the NPG vesicles was found to be 52%. The nano-formulation reveals the
in-vitro
anti-oxidative and anti-inflammatory properties and showed non-toxicity on normal human fibroblast cell line as compared to the parent compound propyl gallate. NPG vesicles showed prominent anti-inflammatory potential against carrageenan induced paw edema and found to be non-toxic in Wistar rats in acute toxicity studies for seven days. In conclusion, nano formulation NPG vesicles showed effective anti-oxidative and anti-inflammatory effects both
in-vitro
and
in-vivo
and has the efficacy to become a potential modulator for targeted therapy.
Phytochemical studies on the root of Abrus precatorius Linn. (Fabaceae), leads towards the identification of four undescribed (abruquinones M, N, O, and P), and seven known abruquinones, ...(abruquinones A, E, B, F, I, D, and G). Spectroscopic analyses (1D, and 2D NMR, HRESI-MS) were used in elucidating structures of the all compounds. Evaluation of anticancer activities of the isolated isoflavanquinones revealed that abruquinones M, and N showed cytotoxicity against oral CAL-27 (IC50 values 6.48 and 5.26 μM, respectively), and colon (Caco-2) cell lines (IC50 values 15.79 and 10.33 μM, respectively). Abruquinone M also inhibited the growth of lung cancer cells (NCI–H460) with IC50 of 31.33 μM. The isolated isoflavanquiones also showed potent anti-inflammatory potential through phagocyte oxidative burst and pro-inflammatory cytokine TNF-α inhibition in vitro. These findings suggest isoflavanquinones from A. precatorius roots as candidates for further research in cancer treatment.
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•Four unreported isoflavanquinones (1–4) were isolated from the roots of Abrus precatorius.•Compounds 1, 2, 5, and 7 exhibited cytotoxicity against CAL-27, CaCO2, NCI-H460 cancer cells.•The compounds displayed potent TNF- α inhibition and other anti-inflammatory activities.
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•Synthesis of second generation analogs of stylissatin A (STA), SAR established toward inhibition of NO.•STA analog2was identified as more potent NO inhibitor than natural product and ...standard.•Analog 2inhibited the gene expression of pro-inflammatory mediators.
The cyclic peptide stylissatin A(STA) was obtained from the Papua New Guinean marine spongeStylissamassaas a potent nitric oxide (NO) inhibitor.Among its reported analogs,cyclo-{Glu6, Ala2}-STA1potentlyinhibited theinterleukin-2 and proliferation of T-cells indicating position 2 of sequence playing important part in biological activities of this compound.In current studies, second generation analogs of STAwere synthesizedaround its most active analog1by screening position 2 of analog1with different amino acid. All analogs2–6were identified by mass, and NMR techniques.The synthesized analogswere also evaluated against NO generation by lipopolysaccharide (LPS)-stimulated murine J774.2macrophages, ROS inhibition from whole blood phagocytes, and T-cell proliferation from Jurkat cells.All analogswere found to be inactive towards interleukin-2, T-cells proliferation, and ROS inhibition. The analog2showed a potent suppression of NO (IC50 = 46.0 ± 2.2 µM) that was superior to the activityreported for natural product STA.Further attempts to optimizeanalog2afforded new nitric oxide inhibitors2a-2fwhich were found less active than2.The analog2also downregulated the transcription of pro-inflammatory molecules, tumor necrosis factor-α, interlukin-1β, caspase-1 and ASC which further highlights its anti-inflammatory and possible therapeutic potential. Analog2was non-toxic to BJ and Vero cell lines of normal mammalian origin.
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