Oleanolic acid( chèn hình acid này nha)

Oleanolic is a pentacyclic triterpenoid carboxylic acid, and is the major component of some
traditional medicinal herbs, widely distributed in nearly 200 species of plants, including some
socioeconomically important crops, such as olive plants. It can also be isolated from garden
thyme, clove plants, apple, loquat, grape and elderberry.

Oleanolic acid has been found to have several pharmacological actions, including liver
protection, antioxidation, hypolipidemia, anticancer, anti-inflammatory, and antiviral. Oleanolic
acid has limited pharmaceutical development due to its weak water solubility and low oral
bioavailability, making it difficult to effectively utilize its medicinal effects. Different oleanolic
acid dosage forms and derivatives have been devised and synthesized through the application of
contemporary preparation techniques and procedures.

To improve the water solubility and biosorption of oleanolic acid, methods used include:
-Use nanosuspensions of oleanolic acid.
-Using a self-microemulsifying system of oleanolic acid.
-Using micelles to improve the water solubility, dissolution and biosorption of oleanolic acid.

Synthesis of Oleanonic Acid

Oleanolic acid was converted to its corresponding methyl ester by treating it with methyl iodide
and potassium carbonate in DMF. This was followed by oxidation using Dess–Martin periodane
(DMP) reagent in dichloromethane. Hydrolysis of oleanonic acid methyl ester with lithium
chloride was carried out under nitrogen at 50°C for 6 h. This was followed by addition of sodium
carbonate and 3% aqueous HCl. The mixture was extracted with diethyl ether and dried with
sodium sulfate.
(này vẽ quy trình nha)

Pharmacological Effects of OA and Its Derivatives

1.Hepatoprotective Effect.
The hepatoprotective effect of oleanolic acid makes it useful as an over-the-counter oral drug in
China to treat humans for liver disorders. Not only has an oleanolic acid protective effect on
acute chemical liver injury but also it has a protective effect on liver fibrosis and cirrhosis caused
by chronic liver diseases.

2.Antitumor Activity.
OA is one of the most abundant triterpenoids in plants and possesses antitumor activity in many
cancer lines, such as liver cancer, thyroid cancer , lung cancer , cervical cancer, and gastric
cancer. At present, there are many reports on the treatment of liver cancer with OA. Studies have
shown that the inhibition of cancer cell growth by OA is mediated via suppression of cancer cell
migration and invasion, mitochondrial apoptosis
Additionally, research has shown that p-glycoprotein inhibition or the combination of OA and
autophagy inhibitors can have a greater anti-liver cancer impact. OA has a large molecular
weight and low solubility, which results in low anticancer efficiency. As a result, scientists have
created a wide range of OA derivatives, including the hybrid of OA and hederagenin-nitric oxide
donor, 2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oic acid (CDDO), as well as its C-28
modified derivative, methyl-ester (CDDO-Me), and a gold (I) complex that contains an OA
derivative.

3.Anti-Inflammatory Activity.
OA has a strong antiinflammatory impact and is useful against a wide range of inflammations,
including vasculitis, enteritis, and tracheitis. A further investigation discovered a connection
between the anti-inflammatory properties of OA and MAPK signaling pathways. Wang and
colleagues provided evidence that OA therapies could reduce spinal cord injury in a dose-
dependent manner by obstructing the processes of inflammation and apoptosis mediated by p38
and JNK. As a result, OA can be used as a successful therapeutic agent to treat spinal cord
injuries.

4.Other Pharmacological Activities

OA has the antioxidation effect, and its mechanism may be related to the antioxidant’s
generation increase and the expression of oxidative. In addition, OA also has antiosteoporosis,
antiproliferation of prostate cells, antimuscle atrophy, anti-influenza, and antidepression effects.

New Dosage Form of Oleanolic Acid

Cyclodextrin Inclusion.
Through its external hydrophilic and internal hydrophobic structure, cyclodextrin can wrap many
small molecular drugs to improve the water solubility of insoluble drugs. Cyclodextrin is used to
encapsulate many small molecule drugs to improve the water solubility of insoluble drugs.
Studies have shown that the use of cyclodextrin can enhance the solubility of oleanolic acid in
water. Methods include using β-cyclodextrin, hydroxypropyl β-cyclodextrin and its derivatives
to create oleanolic acid compounds, which improve the solubility and bioabsorption of oleanolic
acid.
( cái method để sang 1 slide khác nha, cso hình càng tốt nha)

Solid Dispersion
Solid Dispersion (SD) is a simple method to improve drug dissolution and bioabsorption.
Common carriers for solid dispersions include povidone (pvp), cross-linked povidone (pvpp),
and nano calcium carbonate. Some studies have chosen the PVPk30-Soluplus mixture to prepare
oleanolic acid solid dispersion, which enhances the solubility and dissolution rate of this
ingredient, improving the solubility effect of oleanolic acid.
 Nanometer Preparation.
Nanometer Preparation is the process of using nanosystems such as nanoemulsions,
phospholipid complexes, micelles, and nanoliposomes to improve the solubility and
bioabsorption of oleanolic acid. These methods enhance the anticancer activity and improve the
absorption and distribution of oleanolic acid.

Derivatives of Oleanolic Acid

1.Structural Modification of A Ring and C-28 Position

Improvement of the A-ring structure and esterification of the C-28 position of oleanolic acid
were investigated. These methods include:
-Change the A ring structure and make an oxymeether at the C-3 position.
-Esterizes the C-28 position and replaces the aromatic hydrocarbon at the C-28 carboxyl
position.
-Connecting different pharmacophore groups to study the anticancer activity of oleanolic acid.

2.Structural Modification of C Ring.

The improvement of the C-ring structure of oleanolic acid has been studied. These
methods include:
-Design and synthesis of oleanolic acid derivatives with cinnamate structure.
-Use the same method to synthesize oleanolic acid derivatives with amide
structure.

Conclusion
Preparing new dosage forms and modifying the chemical structure of OA can improve the
bioabsorption and expand the application range, which are two effective ways to design and
develop new drugs. Furthermore, with the increase of drug resistance of some bacteria and
viruses, developing new drugs from natural products has become a research trend, and
pentacyclic triterpenes have attracted much attention. noted for their diverse pharmacological
activities. Notably, oleanolic acid exists widely in nature and has strong biological activity and
great research potential.