**3.4 Biosynthesis of berberine**

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

the plasma level of myocardial enzymes (cardiac troponins (CTn) I and creatine kinase-MB (CKMB)), endothelin (ET), superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), and histological changes of the heart were determined. The outcome was observed that salvianolic acid B significantly increased the plasma levels of CTn I, CKMB, MDA, and ET contents; decrease in T-SOD and NO contents; reduction in infarct size; and improved myocardial ultrastructure. It was concluded that salvianolic acid B has an impact against conditions such as myocardial ischemia–reperfusion injury via the regulation of reducing oxidative stress, active oxygen metabolism, and myocardial apoptosis [84]. A study conducted by [85] also stated that salvianolic acid which is a phenolic could also be effective in alleviating ischemic-reperfusion injury. It could also prevent myocardial ischemia–reperfusion injury through an increased glucose condition by adjusting the NADPH oxidase 2 (Nox2)/reactive oxygen species (ROS)/ phosphorylated-c-Jun N-terminal kinase 2 (p-JNK2)/NF-κB pathway to reduce transient receptor potential cation channel, member 6 (TRPC6)/Ca2+ influx,

Anti-thrombotic effects which are through its actions on blood rheology has also been known to be a possible action of salvianolic acid in *S. miltiorrhiza*. It also acts as to prevent platelet aggregation by targeting P2Y1 or P2Y12 receptors, which are novel target receptors required for anti-platelet aggregation. Salvianolic acid B experimentally, only antagonizes the action of platelet P2Y12 receptors, while

Other studies by [88] have also illustrated that caffeic acid can inhibit plateletmediated thrombosis by P-selectin expression, repression of ADP-induced platelet aggregation, ATP release, and Ca2+ mobilization and attenuate the activation of ERK, p38, JNK, and integrin αIIbβ3. It could also increase cAMP expression levels. Better antiplatelet and anti-thrombotic therapeutic efficacy have also been demonstrated in Danshensu when compared to other constituents. Several contributions have been made through its ability to selectively suppress balancing the ratio of thromboxane A2 (TXA2)/prostacyclin (PGI2) and the expression of

Several studies have been conducted on the anti-liver injury activity of polyphenols and from [90] salvianolic acid B protects liver cells by enhancing lysosome-associated membrane protein 1 (LAMP1) expression and preserving lysosomal membrane integrity through scavenging ROS. Salvianolic A has also been concluded by [91, 92] that it protects acute hepatic injury after inducing mice models with concanavalin A. The outcome of the liver function markers, alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) showed that salvianolic acid A significantly reduced ConA-induced AST and ALT activity. Also, there was a reduction in the hepatotoxic cytokine levels, such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α; improvement in the increased NF-κB level and cleaved caspase-3; and reversal of B-cell lymphoma-extra-large (Bcl-xL)

Wang et al. [90] concluded that salvianolic acid B seems to be effective and safe, and it could develop this natural component into a potential therapeutic agent for the management of glioma. This is because of its inhibitory actions on the human glioma U80 cells, which its initiation leads to p38-activation-mediated ROS

Reviews conducted by Rasouli et al. [93] throws more light on the importance of polyphenols from foods. This because they are beneficial in most health conditions including pernicious human diseases (HDs). Also, people who followed a specific diet particularly polyphenol-rich diets are of lower risk of several ranges of chronic

diseases, such as diabetes, obesity, cancer, and heart disease.

salvianolic acid A and C are P2Y12 and P2Y1 receptor inhibitors [87].

**16**

subfamily C [86].

cyclooxygenase (COX)-2 [89].

expression [79].

production.

Berberine is a quaternary ammonium salt and it's from a group of isoquinoline alkaloids termed 2,3–methylenedioxy-9,10-dimethoxyprotoberberine chloride; C20H18NO4+. It is highly concentrated in the roots, stem bark, rhizomes and of numerous plants including *Rhizoma coptidis, Tinospora cordifolia, Coptis chinensis, Hydrastis canadensis, Berberis vulgaris, Berberis aquifolium, Berberis aristata, Arcangelisia flava* and *Cortex rhellodendri* [94].

Berberine comprises of several derivatives such as berberrubine, jatrorrhizine thalifendine, and demethyleneberberine [94].
