MBARARA UNIVERSITY OF SCIENCE AND TECHNOLOGY

FACULTY OF MEDICINE

DEPARTMENT OF PHARMACY/ PHARMACEUTICAL SCIENCE

COURSE UNIT: DRUG DESIGN AND CLINICAL TRIALS

COURSE CODE: BPH4212 / BPS3213

LECTURER’S NAME: DR EDWARD LUKYAMUZI

GROUP MEMBERS

STUDENT'S NAME REGISTRATION NUMBER

Agaba Ronald 2019/PHA/015/PS
Okalebo Hensley 2019/PHA/115/PS
Melody Masiga Samantha 2020/PHS/---/PS

Topic: Effects of silymarin on metabolic syndrome: a review

QUESTIONS:

1. What need was the research answering (Background and Justification)?

2. What receptors did the lead compound interact with?
3. How did they identify these targets in the study?
4. How did they validate these targets in the study?
5. What was the end point of the study?
6. Comment on the relationship between the receptors and the end point of the study

Background: Metabolic syndrome is defined as abdominal obesity, dyslipidemia (DL),

hypertension (HTN), insulin resistance with or without glucose tolerance, pro-inflammatory
and pro-thrombotic state. It is also one of the rising global health problems and medical
challenges as a result of excess calorie intake, urbanization, and sedentary lifestyle. The
importance of metabolic syndrome is the clinical complications it causes; and as a complex of
risk factors, it is accounted as a predisposing factor for cardiovascular diseases as its primary
outcome. Systemic HTN and abnormal lipid profile may occur due to insulin resistance,
which leads to atherosclerotic vascular disease. Therefore, metabolic syndrome increases the
risk of stroke and myocardial infarction (MI).

Given the serious clinical ramifications of metabolic syndrome, most attention has been
directed toward determining the worthiness of herbal medicines. There are emerging studies
on preventive and therapeutic effects of ‘silymarin’ on different components of metabolic
syndrome. Extracted from the dried seeds of milk thistle plant (Silybum marianum L.),
silymarin has been used in the treatment of different diseases for many years. This plant has
also been used and researched into for its several protective effects on toxicities of different
chemicals, specific organ toxicities such as acrylamide-induced neurotoxicity, and acrolein-
induced cardiotoxicity. Moreover, since silymarin has strong antioxidant and anti-
inflammatory properties, its prophylactic effects have been successfully demonstrated against
radiotherapy-induced mucositis in head and neck cancers, as well as Hand-foot syndrome due
to Capecitabine in patients with gastrointestinal cancers. In general, various mechanisms of
actions have been known for silymarin that will be discussed later.
All available human and experimental papers published from 2012 to date, in which the
effect of ‘silymarin’ on different components of metabolic syndrome had been investigated,
were included in this review.

Justification: The aim of this review is to discuss available human and experimental
researches into the promising effects of silymarin on different elements of metabolic
syndrome.
Receptors: Enterocyte P-glycoprotein (P-gp).

Identification of targets: The amount of berberine capable of crossing enterocytes seems to

be reduced by about 90% by P-gp, and this suggests that either the use of a potential P-gp
inhibitor21 or a chemical modification of berberine that would allow it to overcome P-gp
antagonism22 might enhance its poor oral bioavailability, thus increasing its clinical
effectiveness.

Methods used for target validation: Ex-vivo method using the human intestinal Caco-2 cell
line culture as a model of the intestinal barrier.

End point of the study: To verify, in a larger sample enrolled on the base of a T2DM
diagnosis, whether the addition of 210 mg silymarin to 1,000 mg berberine could improve
upon the antihyperglycemic effect of berberine alone, administered at the same dose of 1,000
mg/day. Berberol (Berberis aristata and Silybum marianum) against those obtained from the
administration of Berberis aristata alone indicates that HbA1c is the parameter that most
benefits from the presence of silymarin. Indeed, glycosylated hemoglobin reduced by 7.2%
approximately following the administration of 1,000 mg berberine and by about 12.3%
following the administration of 1,000 mg berberine and 210 mg silymarin.

The enterocyte apical efflux P-glycoprotein (P-gp) is responsible for apical efflux of several
substances including drugs. Therefore the number of active P-gp affects directly, the
bioavailability of berberine.