WO2018165780A1 - Antioxidant, anti-inflammatory compositions and uses thereof - Google Patents

Antioxidant, anti-inflammatory compositions and uses thereof Download PDF

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WO2018165780A1
WO2018165780A1 PCT/CN2017/000237 CN2017000237W WO2018165780A1 WO 2018165780 A1 WO2018165780 A1 WO 2018165780A1 CN 2017000237 W CN2017000237 W CN 2017000237W WO 2018165780 A1 WO2018165780 A1 WO 2018165780A1
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Prior art keywords
acid
composition
caffeoylshikimic
shikimic
oxidative
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PCT/CN2017/000237
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French (fr)
Inventor
Sambanthamurthi Ravigadevi
Yew Ai Tan
T. G. Sambandan
Kyun Rha CHO
Anthony J. Sinskey
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Malaysian Palm Oil Board
Ye, Tao
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Priority to CN201780000807.7A priority Critical patent/CN109069456A/en
Priority to PCT/CN2017/000237 priority patent/WO2018165780A1/en
Publication of WO2018165780A1 publication Critical patent/WO2018165780A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/191—Carboxylic acids, e.g. valproic acid having two or more hydroxy groups, e.g. gluconic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants

Definitions

  • the present invention relates to compounds having synergistic antioxidant and anti-inflammatory properties. More particularly, the present invention relates to compounds enhancing properties of anti-oxidative and anti-inflammatory agents.
  • Oxidative stress for example, represents an imbalance between the levels of damaging oxidizing species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) .
  • ROS reactive oxygen species
  • RNS reactive nitrogen species
  • Oxidative stress and inflammation are implicated in the pathogenesis of metabolic diseases, diabetes, obesity, dyslipidemia and their associated cardiovascular complications. Oxidative stress is also associated with a wide range of diseases and other medical conditions such as Aizheimer′sdisease, Parkinson′sdisease, rheumatoid arthritis, neurodegeneration, airway inflammation and hyper-responsiveness (e.g. asthma) , and some skin disorders, such as vitiligo. In addition to pathological conditions, oxidative stress is also known to be involved in some undesired components of aging.
  • cytokines such as TNFa, IL6, and IL18.
  • mitochondria generate cellular energy through TCA cycle activity and the associated electron transport chain of the inner mitochondrial membrane.
  • ROS reactive oxygen species
  • RNS reactive nitrogen species
  • the cells are equipped with several antioxidant enzymes to neutralize ROS and RNS.
  • antioxidant enzymes to neutralize ROS and RNS.
  • damage most likely occurs when the ROS is excessive and/or anti-oxidant pathways are overwhelmed.
  • lowering the oxidative stress leads to improvement in the disease manifestation. In many other cases, lowering the oxidative stress may prevent the disease outbreak.
  • phenolic anti-oxidants vis caffeoylshikimic acid, p-hydroxybenzoic acid in compositions, such as Oil Palm Phenolics (OPP) are responsible for the anti-oxidative and anti-inflammatory activity.
  • OPP Oil Palm Phenolics
  • phenolic compounds have been shown to be strong antioxidants, comparable with many known reducing molecules in several assays (Bala Balasundram et. al (2005) : “Antioxidant properties of palm fruit extracts” , Asia Pacific Journal of Clinical Nutrition, 14 (4) , 319-324) .
  • Gene expression studies have also shown the anti-oxidative and anti-inflammatory effects of Oil Palm Phenolics in mammalian cells (Sarnbanthamurthi R. et al. (2013) : “OPP attenuate changes caused by an atherogcnic diet in mice” , European Journal of Nutrition, 52 (2) , 443-456) .
  • compositions comprising oil palm phenolics and shikimic acid or derivatives thereof.
  • the present invention further provides use of shikimic acid or derivatives thereof to enhance anti-oxidative properties of anti-oxidative agents.
  • the present invention further provides a method of ameliorating oxidative stress or inflammation comprising: administering to a subject a therapeutically effective amount of a composition comprising oil palm phenolics and shikimic acid or derivatives thereof.
  • the present invention further provides use of a composition comprising shikimic acid and 3-dehydroshikimic acid in ameliorating oxidative stress, inflammation or related disorders.
  • FIG. 1 is a graphical representation of the biological enhancement of chemical combination of major compounds of Oil Palm phenolics in cell-based NO2 - scavenging activity (Griess assay, RAW macrophages, Mean ⁇ SE) .
  • compositions comprising oil palm phenolics and shikimic acid or derivatives thereof.
  • shikimic acid derivatives include 3-dehydroshikimic acid.
  • oil palm phenolics are selected from protocatechuic acid, p-hydroxybcnzoic acid, 4-caffeoylshikimic acid, 3-eaffecylshikimic acid, 5-caffeoylshikimic acid or mixtures thereof.
  • the composition optionally comprises bioactive compounds selected from the group consisting of peptides, minerals, oligosaccharides and mixtures thereof.
  • the composition further comprises pharmaceutically acceptable carriers.
  • the composition optionally comprises one or more diluents.
  • diluents include dextrose, maltodextrin, saline, buffered saline, water, glycerol and ethanol.
  • composition of the present invention comprising oil palm phenolics may also comprise more than one component of other anti-oxidative stress and/or anti-inflammatory agents such as drugs, quasi-drugs, foods or beverages used for this purpose.
  • composition of the present invention may be formulated in any form.
  • the formulation can be prepared as injectable preparation (true solution, suspension, or emulsion) , oral dosage form (tablet, capsule, soft capsule, aqueous medicine, pill, granule, ) topical preparation (ointment, patch, spray, solutioa, and the like.
  • the composition is applied topically, as a skin dermal patch, as a skin spray or as a nasal or intravenous solution.
  • the present invention relates to use of shikimic acid or derivatives thereof to enhance anti-oxidative properties of anti-oxidative agents.
  • the anti-oxidative agents are oil palm phenolies selected from the group comprising of protocatechuic acid, p-hydroxybenzoic acid, 4-caffeoylshikimic acid, 3 -eaffecylshikimic acid, 5-caffeoylshikimic acid and mixtures thereof.
  • the present invention relates to use of shikimic acid or derivatives thereof to enhance anti-inflammatory properties of anti-inflammatory agents.
  • the anti-inflammatory agents are oil palm phenolics selected from the group comprising of protocatechulc acid, p-hydroxybenzoic acid, 4-caffeoylshikimic acid, 3 -eaffecylshikimic acid, 5-caffeoylshikimic acid and mixtures thereof.
  • the present invention provides a method of ameliorating oxidative stress or inflammation comprising: administering to a subject a therapeutically effective amount of the composition as claimed in claim 1.
  • the composition inhibits nitrite in biological systems.
  • the composition inhibits ROS (Reactive Oxygen Species) in biological systems.
  • the composition is appliedtopically, as a skin dermal patch, as a skin spray or as a nasal or intravenous solution.
  • the present invention further relates to use of a composition comprising shikimic acid and 3-dehydroshikimic acid in ameliorating oxidative stress, inflammation or related disorders.
  • Protocatechuic acid (P) Protocatechuic acid
  • SNP in aqueous solution at physiological pH spontaneously generates nitric oxide, which interacts with oxygen to produce a nitrite ion that can be estimated by using griess reagent.
  • Red blood cells can be used as a cellular model to quantify reactive oxygen species (ROS) . As these cells lose their nuclei at the erythroblast stage, they cannot perform transcription and translation for bringing about genetic and protein level changes. Hence, the ROS measurement signifies the ability of the antioxidant compound to enter the cytosol and quench free radicals.
  • ROS reactive oxygen species
  • Shikimic acid shows inhibitory action in the two assays that measure the anti-inflammatory and anti-oxidative activity: 1) Cell-based griess assay 2) Cell-based PMN assay and the nitrite scavenging assay: 3) Chemical-based SNP assay.
  • it is able to enhance the anti-inflammatory and anti-oxidative activity of other components only in the two cell-based assays (Griess and PMN) .
  • RBC cells shows no activity as it lacks direct antioxidant activity.
  • 3-dehydroshikirnic acid shows inhibitory action in the three assays that measure the anti-inflammatory and anti-oxidative activity: 1) Cell-based gricss assay 2) Cell-based PMN assay 3) Cell-based CAP-e assay and the nitrite scavenging assay: 4) Chemical-based SNP assay.
  • Cell-based gricss assay 2 Cell-based PMN assay 3
  • Cell-based CAP-e assay the nitrite scavenging assay
  • Chemical-based SNP assay Chemical-based SNP assay.
  • its enhancement effect could be seen in 1) cell-based griess assay 2) Cell-based PMN assay 3) Cell-based CAP-e assay and 4) the chemical-based ORAC assay.
  • FIG. 1 and Table 2 show the synergistic effect of the composition in cell based nitrite scavenging activity.
  • PH435 composition was prepared according to the concentration present in 800 ⁇ g/mL of Oil Palm Phenolics. From FIG, 1 and Table 2 (below) , it can be seen that the nitrite scavenging activity of the combinations of Protocatechuic acid, p-hydoxybenzoic acid, 4-caffeoylshikimic acid, 3-caffeoylshikimic acid with 3-dehydroshikiinic acid and Shikimic acid is significantly higher than the composition of Oil palm phenolics.
  • AMP nucleotide Adenosine Monophosphate
  • shikimic acid may be requirexl by shikimic acid in order to exhibit its enhancement effect. Attaining such a structure is only possible in a cell-based system. It may also be possible that shikimic acid cannot get converted into its active form 3-dehydroshikimic acid in RBC cells due to lack of GDH, but the conversion can be possible in granulocytes. It could also be a result of the anti-inflammatory and anti-oxidative signaling actions by shikimic acid in combination with other components.

Abstract

Compositions comprising oil palm phenolics and shikimic acid or derivatives thereof and their use in enhancing anti-oxjdative and anti-inflammatory properties.

Description

ANTIOXIDANT， ANTI-INFLAMMATORY COMPOSITIONS AND USES THEREOF
FIELD OF INVENTION
The present invention relates to compounds having synergistic antioxidant and anti-inflammatory properties. More particularly， the present invention relates to compounds enhancing properties of anti-oxidative and anti-inflammatory agents.
BACKGROUND OF THE INVENTION
The normal functioning of life requires， inter alia， proper balance between formation and elimination of damaging substances. Oxidative stress， for example， represents an imbalance between the levels of damaging oxidizing species， such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) . The insufficient ability of a biological system to readily neutralize or eliminate the oxidizing species leads to deleterious modifications of cellular proteins， lipids and DNA.
Oxidative stress and inflammation are implicated in the pathogenesis of metabolic diseases， diabetes， obesity， dyslipidemia and their associated cardiovascular complications. Oxidative stress is also associated with a wide range of diseases and other medical conditions such as Aizheimer′sdisease， Parkinson′sdisease， rheumatoid arthritis， neurodegeneration， airway inflammation and hyper-responsiveness (e.g. asthma) ， and some skin disorders， such as vitiligo. In addition to pathological conditions， oxidative stress is also known to be involved in some undesired components of aging.
As to inflammation， clinical studies suggest that acute hyperglycemia results in elevated levels of circulating inflammatory cytokines such as TNFa， IL6， and IL18. During hyperglycemia and/or hyperlipidemia， mitochondria generate cellular energy through TCA cycle activity and the associated electron transport chain of the inner mitochondrial membrane. However， while mitochondria generate elevated ATP production， mitochondria can also generate significant reactive oxygen species (ROS) and reactive nitrogen species (RNS) .
The cells are equipped with several antioxidant enzymes to neutralize ROS and RNS. However， while cells have a number of available anti-oxidant mechanisms， damage most likely occurs when the ROS is excessive and/or anti-oxidant pathways are overwhelmed.
In many cases， lowering the oxidative stress leads to improvement in the disease manifestation. In many other cases， lowering the oxidative stress may prevent the disease outbreak.
In our own earlier work， we have shown that phenolic anti-oxidants vis caffeoylshikimic acid， p-hydroxybenzoic acid in compositions， such as Oil Palm Phenolics (OPP) ， are responsible for the anti-oxidative and anti-inflammatory activity. For e.g. phenolic compounds have been shown to be strong antioxidants， comparable with many known reducing molecules in several assays (Bala Balasundram et. al (2005) ： “Antioxidant properties of palm fruit extracts” ， Asia Pacific Journal of Clinical Nutrition， 14 (4) ， 319-324) . Gene expression studies have also shown the anti-oxidative and anti-inflammatory effects of Oil Palm Phenolics in mammalian cells (Sarnbanthamurthi R. et al. (2013) ： “OPP attenuate changes caused by an atherogcnic diet in mice” ， European Journal of Nutrition， 52 (2) ， 443-456) .
However， there still remains a need in the art for enhancing the treatment of metabolic disorders by way of ameliorating the inflammatory and oxidative processes associated with such disorders.
SUMMARY OF THE INVENTION
Various embodiments of the present invention provide a composition comprising oil palm phenolics and shikimic acid or derivatives thereof.
The present invention further provides use of shikimic acid or derivatives thereof to enhance anti-oxidative properties of anti-oxidative agents.
The present invention further provides a method of ameliorating oxidative stress or inflammation comprising： administering to a subject a therapeutically effective amount of a composition comprising oil palm phenolics and shikimic acid or derivatives thereof.
The present invention further provides use of a composition comprising shikimic acid and 3-dehydroshikimic acid in ameliorating oxidative stress， inflammation or related disorders.
BRIEF DESCRIPTION OF THE DRAWINGS
Other objects， features， and advantages of the invention will be apparent from the following description when read with reference to the accompanying drawings.
FIG. 1 is a graphical representation of the biological enhancement of chemical combination of major compounds of Oil Palm phenolics in cell-based NO2- scavenging activity (Griess assay， RAW macrophages， Mean ± SE) .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention will now be described in detail with reference to the accompanying in drawings.
Various embodiments of the present invention provide a composition comprising oil palm phenolics and shikimic acid or derivatives thereof.
According to an embodiment of the invention， shikimic acid derivatives include 3-dehydroshikimic acid.
According to another embodiment of the present invention， oil palm phenolics are selected from protocatechuic acid， p-hydroxybcnzoic acid， 4-caffeoylshikimic acid， 3-eaffecylshikimic acid， 5-caffeoylshikimic acid or mixtures thereof.
According to yet another embodiment of the present invention， the composition optionally comprises bioactive compounds selected from the group consisting of peptides， minerals， oligosaccharides and mixtures thereof.
According to an embodiment of the present invention， the composition further comprises pharmaceutically acceptable carriers.
According to an embodiment， the composition optionally comprises one or more diluents. Non-limiting examples of diluents include dextrose， maltodextrin， saline， buffered saline， water， glycerol and ethanol.
The composition of the present invention comprising oil palm phenolics may also comprise more than one component of other anti-oxidative stress and/or anti-inflammatory agents such as drugs， quasi-drugs， foods or beverages used for this purpose.
The composition of the present invention may be formulated in any form. The formulation can be prepared as injectable preparation (true solution， suspension， or emulsion) ， oral dosage form (tablet， capsule， soft capsule， aqueous medicine， pill， granule， ) topical preparation (ointment， patch， spray， solutioa， and the like.
According to an embodiment， the composition is applied topically， as a skin dermal patch， as a skin spray or as a nasal or intravenous solution.
According to an embodiment， the present invention relates to use of shikimic acid or derivatives thereof to enhance anti-oxidative properties of anti-oxidative agents.
According to another embodiment of the present invention， the anti-oxidative agents are oil palm phenolies selected from the group comprising of protocatechuic acid， p-hydroxybenzoic acid， 4-caffeoylshikimic acid， 3 -eaffecylshikimic acid， 5-caffeoylshikimic acid and mixtures thereof.
According to yet another embodiment， the present invention relates to use of shikimic acid or derivatives thereof to enhance anti-inflammatory properties of anti-inflammatory agents.
According to another embodiment of the present invention， the anti-inflammatory agents are oil palm phenolics selected from the group comprising of protocatechulc acid， p-hydroxybenzoic acid， 4-caffeoylshikimic acid， 3 -eaffecylshikimic acid， 5-caffeoylshikimic acid and mixtures thereof.
According to still another embodiment， the present invention provides a method of ameliorating oxidative stress or inflammation comprising： administering to a subject a therapeutically effective amount of the composition as claimed in claim 1.
According to an embodiment of the present invention， the composition inhibits nitrite in biological systems.
According to an embodiment of the present invention， the composition inhibits ROS (Reactive Oxygen Species) in biological systems.
According to an embodiment of the present invention， the composition is appliedtopically， as a skin dermal patch， as a skin spray or as a nasal or intravenous solution.
According to an embodiment， the present invention further relates to use of a composition comprising shikimic acid and 3-dehydroshikimic acid in ameliorating oxidative stress， inflammation or related disorders.
The following examples are provided to illustrate certain particular features and/or embodiments. These examples should not be construed to limit the disclosure to the particular features or embodiments disclosed therein
EXAMPLES
For the sake of convenience， the following abbreviations will be used in the following examples：
Abbreviations-
Protocatechuic acid (P) ；
p-hydoxybenzoic acid (H) ；
3-dehydroshikiinic acid (D) ；
caffeoylshikimic acid (C) ；
4-caffeoylshikimic acid (4) ；
3-caffeoylshikimic. acid (3) ；
5-caffeoylshikimic acid (5) ；
Shikimic acid (S)
Chemical combination of PH435 and S (PH435S) ；
Chemical combination of PH435 and D (PH435D) ；
Mathematical sum of ％inhibition of NO2 - (PH435+S) ；
Mathematical sum of％inhibition of NO2 - (PH435+D)
EXAMPLE 1
Nitrite measurement (Sodium nitroprusside -SNP assay)
SNP in aqueous solution at physiological pH spontaneously generates nitric oxide， which interacts with oxygen to produce a nitrite ion that can be estimated by using griess reagent.
In this assay， shikimic acid and 3-dehydroshikimic acid exhibit a low inhibition of the nitrite ion
However， it does not show any enhancement when added along with p-hydroxybenzoic acid， the compound that is present in large quantity in OPP. 3-dehydroshikimie acid， exhibited a similar effect as shikimic acid in this chemical system. This result may be because the assay measures only the chemical activity.
The 4 combinations of OPP， PH435， PH435S， PH435D were found to exhibit very similar percentages of nitrite inhibition， without any enhancement by shikimic acid and 3-dehydroshikirnic acid.
Cell-based systems：
EXAMPLE 2
H2O2 measurement (Cell-based antioxidant protection in erythrocytes CAP-e assay)
Red blood cells can be used as a cellular model to quantify reactive oxygen species (ROS) . As these cells lose their nuclei at the erythroblast stage， they cannot perform transcription and translation for bringing about genetic and protein level changes. Hence， the ROS measurement signifies the ability of the antioxidant compound to enter the cytosol and quench free radicals.
In this method， shikimic acid does not show any effect on reducing ROS. However， all the other compounds are able to inhibit H2O2 oxidation. Both HCS and HCD combinations are synergistic as they are greater than H+C+S and H+C+D respectively. An interesting observation is that the chemical combination of HCS， the predominant compounds of OPP， is able to explain only 78％of the inhibition of ROS by ON) . However， when 3-de. hydroshikimic acid is added along with H and C， it leads to 93％inhibition of ROS when compared to OPP. The results are shown in Table 1 below：
TABLE 1 Cell-based ROS scavenging activity (CAP-e assay)
TABLE 1
Figure PCTCN2017000237-appb-000001
#Components were added according to the concentration present in 10 mg/mL of OPP.
*All values show statistical significance in comparison to OPP (P ＜0.01， Tukey-Kramer Honestly Significant Differences test)
EXAMPLE 3
H2O2 measurement (Cell-based antioxidant protection in granulocytesipolymor-phonuclear-PMN cells assay)
Shikimic acid shows inhibitory action in the two assays that measure the anti-inflammatory and anti-oxidative activity： 1) Cell-based griess assay 2) Cell-based PMN assay and the nitrite scavenging assay： 3) Chemical-based SNP assay. However， it is able to enhance the anti-inflammatory and anti-oxidative activity of other components only in the two cell-based assays (Griess and PMN) . In RBC cells， it shows no activity as it lacks direct antioxidant activity.
3-dehydroshikirnic acid shows inhibitory action in the three assays that measure the anti-inflammatory and anti-oxidative activity： 1) Cell-based gricss assay 2) Cell-based PMN assay 3) Cell-based CAP-e assay and the nitrite scavenging assay： 4) Chemical-based SNP assay. However， its enhancement effect could be seen in 1) cell-based griess assay 2) Cell-based PMN assay 3) Cell-based CAP-e assay and 4) the chemical-based ORAC assay.
FIG. 1 and Table 2 show the synergistic effect of the composition in cell based nitrite scavenging activity.
For the study， PH435 composition was prepared according to the concentration present in 800μg/mL of Oil Palm Phenolics. From FIG， 1 and Table 2 (below) ， it can be seen that the nitrite scavenging activity of the combinations of Protocatechuic acid， p-hydoxybenzoic acid， 4-caffeoylshikimic acid， 3-caffeoylshikimic acid with 3-dehydroshikiinic acid and Shikimic acid is significantly higher than the composition of Oil palm phenolics.
TABLE 2
Figure PCTCN2017000237-appb-000002
Figure PCTCN2017000237-appb-000003
Components were added according to the concentration present in 800 lμg/mL of OPP
*All components except PH435S show statistical significance (p ＜ 0.05) with respect to OPP using Tukey-Kramer’s Honestly Significant Difference (HSD)
It can be deduced that the presence of AMP (nucleotide Adenosine Monophosphate) as part of its structure may be requirexl by shikimic acid in order to exhibit its enhancement effect. Attaining such a structure is only possible in a cell-based system. It may also be  possible that shikimic acid cannot get converted into its active form 3-dehydroshikimic acid in RBC cells due to lack of GDH， but the conversion can be possible in granulocytes. It could also be a result of the anti-inflammatory and anti-oxidative signaling actions by shikimic acid in combination with other components.
It is to be understood that various modifications and changes may be made or various alternative standard /conventional procedures may be employed without departing from the spirit and sc ope of the present invention and the same should be construed to be within the scope of the present invention.

Claims (15)

  1. A composition comprising oil palm phenolics and shikimic acid or derivatives thereof.
  2. The composition of claim 1， wherein shikimic acid derivatives include 3-dehydroshikimic acid.
  3. The composition of claim 1， wherein oil palm phenolics are selected from protocatechuic acid， p-hydroxybenzoic acid， 4-caffeoylshikimic acid， 3-eaffecylshikimic acid， 5-caffeoylshikimic acid or mixtures thereof.
  4. The composition of claim 1， optionally comprising bioactive compounds selected from the group consisting ofpeptides， minerals， oligosaccharides and mixtures thereof.
  5. The composition of claim 1， further comprising pharmaceutic ally acceptable carriers.
  6. The composition of claim 1， wherein the composition is applied topically， as a skin dermal patch， as a skin spray or as a nasal or intravenous solution.
  7. Use of shikimic acid or derivatives thereof to enhance anti-oxidative properties of anti-oxidative agents.
  8. The use as claimed in claim 8， wherein the anti-oxidative agents are oil palm phenolics selected from the group comprising of protocatechuic acid， p-hydroxybenzoic acid， 4-caffeoylshikimic acid， 3-eaffecylshikimic acid， 5-caffeoylshikimic acid and mixtures thereof.
  9. Use of shikimic acid or derivatives thereof to enhance anti-inflammatory properties of anti-inflammatory agents.
  10. The use as claimed in claim 10， wherein the anti-inflammatory agents are oil palm phenolics selected from the group comprising of protocatechuic acid， p-hydroxybenzoic acid， 4-caffeoylshikimic acid， 3-eaffecylshikimic acid， 5-caffeoylshikimic acid and mixtures thereof.
  11. A method of ameliorating oxidative stress or inflammation comprising： administering to a subject a therapeutically effective amount of the composition as claimed in claim 1.
  12. The method according to claim 12， wherein the composition inhibits nitrite in biological systems.
  13. The method according to claim 12， wherein the composition inhibits ROS (Reactive Oxygen Species) in biological systems.
  14. The method of claim 12， wherein the composition is applied topically， as a skin dermal patch， as a skin spray or as a nasal or intravenous solution.
  15. Use of a composition comprising shikimic acid and 3-dehydroshikimic acid in ameliorating oxidative stress， inflammation or related disorders.
PCT/CN2017/000237 2017-03-17 2017-03-17 Antioxidant, anti-inflammatory compositions and uses thereof WO2018165780A1 (en)

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