trans-Isoferulic acid

Isoferulic acid, a new anti-glycation agent, inhibits fructose- and glucose-mediated protein glycation in vitro.[Pubmed: 23722732]

Molecules. 2013 May 30;18(6):6439-54.

The inhibitory activity of Isoferulic acid (IFA) on fructose- and glucose-mediated protein glycation and oxidation of bovine serum albumin (BSA) was investigated.
METHODS AND RESULTS:
Our data showed that IFA (1.25-5 mM) inhibited the formation of fluorescent advanced glycation end products (AGEs) and non-fluorescent AGE [Nε-(carboxymethyl) lysine: CML], as well as the level of fructosamine. IFA also prevented protein oxidation of BSA indicated by decreasing protein carbonyl formation and protein thiol modification. Furthermore, IFA suppressed the formation of β-cross amyloid structures of BSA.
CONCLUSIONS:
Therefore, IFA might be a new promising anti-glycation agent for the prevention of diabetic complications via inhibition of AGEs formation and oxidation-dependent protein damage.

Evaluation of antioxidant activity of isoferulic acid in vitro.[Pubmed: 21941899]

Nat Prod Commun. 2011 Sep;6(9):1285-8.

Isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA), the isomer of ferulic acid (4-hydroxy-3-methoxycinnamic acid), is a rare phenolic acid occurring in Rhizoma Cimicifugae. Unlike ferulic acid, which has been well investigated, the antioxidant activity of IFA has not been measured.
METHODS AND RESULTS:
In this study, IFA was systematically evaluated for its in vitro antioxidant activity for the first time. IC50 values were calculated of 7.30 +/- 0.57, 4.58 +/- 0.17, 1.08 +/- 0.01, 8.84 +/- 0.43, 7.69 +/- 0.39, 1.57 +/- 0.2, 13.33 +/- 0.49 microg/mL, respectively, for lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl radical) and ABTS (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt) radical scavenging, reducing power on Fe3+ and CU2+ ions, and hydroxyl and superoxide anion radical scavenging. Comparison with the IC50 values with those of the positive controls, Trolox and butylated hydroxyanisole (BHA), it can be concluded that Isoferulic acid is an effective natural antioxidant in both lipid and aqueous media.

Inhibitory effect of ferulic acid and isoferulic acid on murine interleukin-8 production in response to influenza virus infections in vitro and in vivo.[Pubmed: 7617763 ]

Planta Med. 1995 Jun;61(3):221-6.

We investigated the effect of ferulic acid (FA) and Isoferulic acid (IFA), which are active components of the rhizoma of Cimicifuga species used frequently as anti-inflammatory drugs in Japanese Oriental medicines, on murine interleukin-8 (IL-8) production in response to influenza virus infections in vitro and in vivo by antibody-sandwich enzyme-linked immunosorbent assay.
METHODS AND RESULTS:
In the in vitro study, the murine macrophage cell line RAW 264.7 was infected with influenza virus at a dose of 10 plaque forming units (PFU)/cell and cultured in the presence or absence of drugs. Both FA and IFA reduced the IL-8 levels in the 20-h conditioned medium in comparison with control in a dose-dependent manner. The effect of IFA was greater than that of FA: IL-8 levels were reduced to 43% and 56% of the control in the presence of 100 micrograms/ml of IFA and FA, respectively. In the in vivo study, mice were infected with 1,000 PFU of virus and received daily oral administrations of Cimicifuga heracleifolia extract (5 mg/mouse/day), FA (0.5 mg/mouse/day), IFA (0.125 mg/mouse/day), or phosphate buffered saline. The three drugs showed a tendency to reduce IL-8 levels in bronchoalveolar lavage (BAL) obtained 2 days after infection. Moreover, both FA and IFA also significantly reduced the number of exuded neutrophils into BAL. However, the drug administrations did not affect the virus yields in BAL.
CONCLUSIONS:
These data suggest that FA and IFA are novel and potent inhibitors of murine IL-8 production and might act as one of the main components of anti-inflammatory rhizoma of Cimicifuga species.

Anticancer Candidates Derived from Natural Cinnamic Acids.[Pubmed: 25634446]

Anticancer Agents Med Chem. 2015;15(8):980-7.

Cancer is the most dangerous disease that causes deaths all over the world. Natural products have afforded a rich source of drugs in a number of therapeutic fields including anticancer agents. Many significant drugs have been derived from natural sources by structural optimization of natural products. Cinnamic acid has gained great interest due to its antiproliferative, antioxidant, antiangiogenic and antitumorigenic potency.
METHODS AND RESULTS:
Currently, cinnamic acid and its analogs such as caffeic acid, sinapic acid, ferulic acid, and isoferulic acid(3-Hydroxy-4-methoxycinnamic acid) display various pharmacological activities, such as immunomodulation, anti-inflammation, anticancer and antioxidant. They have served as a major source of potential anticancer lead compounds.
CONCLUSIONS:
In this review, we focus on the anticancer potency of cinnamic acid derivatives and novel strategies for the design of these derivatives. We hope this review will be useful for researchers who are interested in developing anticancer agents.

Evaluation of antioxidant activity of isoferulic acid in vitro.[Pubmed: 21941899]

Nat Prod Commun. 2011 Sep;6(9):1285-8.

Isoferulic acid (3-Hydroxy-4-methoxycinnamic acid, IFA), the isomer of ferulic acid (4-hydroxy-3-methoxycinnamic acid), is a rare phenolic acid occurring in Rhizoma Cimicifugae. Unlike ferulic acid, which has been well investigated, the antioxidant activity of 3-Hydroxy-4-methoxycinnamic acid has not been measured.
METHODS AND RESULTS:
In this study, 3-Hydroxy-4-methoxycinnamic acid was systematically evaluated for its in vitro antioxidant activity for the first time. IC50 values were calculated of 7.30 +/- 0.57, 4.58 +/- 0.17, 1.08 +/- 0.01, 8.84 +/- 0.43, 7.69 +/- 0.39, 1.57 +/- 0.2, 13.33 +/- 0.49 microg/mL, respectively, for lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl radical) and ABTS (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt) radical scavenging, reducing power on Fe3+ and CU2+ ions, and hydroxyl and superoxide anion radical scavenging.
CONCLUSIONS:
Comparison with the IC50 values with those of the positive controls, Trolox and butylated hydroxyanisole (BHA), it can be concluded that 3-Hydroxy-4-methoxycinnamic acid is an effective natural antioxidant in both lipid and aqueous media.

Kinetics governing the inhibitory effect of 3-hydroxy-4-methoxycinnamic acid on tyrosinase-catalyzed reactions[Reference: WebLink]

Search for novel histone deacetylase inhibitors. Part II: design and synthesis of novel isoferulic acid derivatives.[Pubmed: 24702857]

Kinetics of inhibitory effect of isoferulic acid on mushroom tyrosinase.[Pubmed: 23931087]

J Cosmet Sci. 2013 Jul-Aug;64(4):235-41.

A study on the kinetics of inhibitory effect of Isoferulic acid on the monophenolase and diphenolase activity of mushroom tyrosinase was carried out using enzymological kinetic analysis method in a Na2HPO4-NaH2PO4 buffer solution (pH = 6.8) at 30°C.
METHODS AND RESULTS:
It was found that Isoferulic acid efficiently inhibits both monophenolase and diphenolase activities of mushroom tyrosinase under experimental conditions. Concentrations of Isoferulic acid leading to 50% rate inhibition (IC50) on monophenolase and diphenolase activity were calculated to be 0.13 mmol/L and 0.39 mmol/L, respectively, which are much lower than that of arbutin (IC50 = 5.3 mmol/L for diphenolase activity). The presence of Isoferulic acid also prolongs the lag period in the oxidation process of l-tyrosine via tyrosinase-a 4.3-min lagging was observed with the presence of 0.20 mmol/L Isoferulic acid-compared to a 1.1-min lagging in the absence of Isoferulic acid. The Lineweaver-Burk plot demonstrates a competitive behavior of Isoferulic acid in the tyrosinase oxidation of l-3,4-dihydroxyphenylalanine, with maximum reaction rate (vm) and inhibition constant (KI) at 64.5 µM/min and 0.11 mmol/L, respectively.

Bioorg Med Chem. 2014 May 1;22(9):2707-13.

Previously, we described the discovery of potent ferulic acid-based histone deacetylase inhibitors (HDACIs) with halogeno-acetanilide as novel surface recognition moiety (SRM).
METHODS AND RESULTS:
In order to improve the affinity and activity of these HDACIs, twenty seven Isoferulic acid derivatives were described herein. The majority of title compounds displayed potent HDAC inhibitory activity. In particular, IF5 and IF6 exhibited significant enzymatic inhibitory activities, with IC50 values of 0.73 ± 0.08 and 0.57 ± 0.16 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against human cancer cells. Especially, IF6 displayed promising profile as an antitumor candidate with IC50 value of 3.91 ± 0.97 μM against HeLa cells.
CONCLUSIONS:
The results indicated that these Isoferulic acid derivatives could serve as promising lead compounds for further optimization.

Modern Food Science & Technology, 2015, 31(4):192-6.

METHODS AND RESULTS:
The kinetics governing the inhibitory effect of 3-Hydroxy-4-methoxycinnamic acid on the activities of monophenolase and diphenolase in tyrosinase were studied using an enzymological kinetic analysis method, in a Na2HPO4-NaH2PO4 buffer system (pH=6.8) at 30℃. The 3-Hydroxy-4-methoxycinnamic acid was observed to efficiently inhibit tyrosinase monophenolase and diphenolase activities. Approximately 0.13 mmol/L and 0.39 mmol/L 3-Hydroxy-4-methoxycinnamic acid caused a 50% rate inhibition (IC50) in monophenolase and diphenolase activities, respectively; these values were much lower than that of arbutin (IC50=5.3 mmol/L for diphenolase activity). The presence of 3-Hydroxy-4-methoxycinnamic acid also prolonged the lag period of monophenolase; the presence of 0.20 mmol/L 3-Hydroxy-4-methoxycinnamic acid resulted in a lag period of 4.3 min, compared to the 1.1 min lag period of monophenolase in the absence of 3-Hydroxy-4-methoxycinnamic acid. The inhibition of diphenolase by 3-Hydroxy-4-methoxycinnamic acid appeared to be reversible.
CONCLUSIONS:
This indicated that the inhibitor suppresses the enzyme activity, resulting in a reduction in catalysis efficiency, as opposed to removing the effective enzyme, which leads to a reduction in enzyme activity. The Lineweaver-Burk plot demonstrated the competitive inhibition of tyrosinase by 3-Hydroxy-4-methoxycinnamic acid, with a maximum reaction rate (vm) and inhibition constant (KI) of 64.5 μmol/min and 0.11 mmol/L, respectively.

Antihyperglycemic action of isoferulic acid in streptozotocin-induced diabetic rats.[Pubmed: 10683186]

Br J Pharmacol. 2000 Feb;129(4):631-6.

Wistar rats with streptozotocin-induced diabetes (STZ-diabetic rats), which is similar to human insulin-dependent diabetic mellitus (IDDM), were employed to investigate the antihyperglycemic action of Isoferulic acid.
METHODS AND RESULTS:
A single intravenous injection of Isoferulic acid decreased the plasma glucose in a dose-dependent manner in the STZ-diabetic rats. Repeated intravenous administration of STZ-diabetic rats with Isoferulic acid (5.0 mg kg(-1)) also resulted in the lowering of plasma glucose after one day. Stimulatory effects of Isoferulic acid on the glucose uptake and glycogen synthesis in soleus muscles isolated from STZ-diabetic rats were also obtained indicating an increase of glucose utilization following Isoferulic acid treatment which was not dependent on insulin. The mRNA level of glucose transporter subtype 4 form (GLUT4) in soleus muscle was raised by Isoferulic acid after repeated treatment for 1 day in STZ-diabetic rats. Similar repeated treatment with Isoferulic acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. However, expression of GLUT4 and PEPCK genes in nondiabetic rats were not influenced by similar treatment with Isoferulic acid.
CONCLUSIONS:
These results suggest that Isoferulic acid can inhibit hepatic gluconeogenesis and/or increase the glucose utilization in peripheral tissue to lower plasma glucose in diabetic rats lacking insulin.