Notes for webinar. Combating the effects of p.acnes.

1. Biofilms
Retinoids
Agents that control cellular proliferation and differentiation within the
pilosebaceous gland may have an effect. Topical retinoids normalise
desquamation within the follicle and decrease inflammation. Retinoids work
by altering the biofilm. Retinoids have anti-androgen properties as well. They
inhibit retinol dehydrogenase-4, which converts 3-alpha-androstenadiol into
DHT.
BPO
BPO is a powerful generator of free radicals, capable of oxidizing proteins in
the bacterial cell wall.
Products that form for oxygen radicals appear to significantly alter the
microenvironment in which the biofilm matrix resides. BPO exerts its action
by the production of free radicals that are bactericidal against both aerobic
and anaerobic organisms. The free benzoloxy radicals are believed to inhibit
metabolic function, alter protein synthesis, induce ornithine decarboxylase
activity, break DNA strands, suppress DNA synthesis and interfere with
mitochondrial respiration.
The combination of BPO with a tertiary amine results in greater radical
activity.
Products that form for oxygen radicals appear to significantly alter the
microenvironment in which the biofilm matrix resides. BPO exerts its action
by the production of free radicals that are bactericidal against both aerobic
and anaerobic organisms. The free benzoloxy radicals are believed to inhibit
metabolic function, alter protein synthesis, induce ornithine decarboxylase
activity, break DNA strands, suppress DNA synthesis and interfere with
mitochondrial respiration.
The combination of BPO with a tertiary amine results in greater radical
activity.
Acids
Prevent attachment of the biofilm to the wall.
Resveratrol
Resveratrol,- eradicates the biofilm. The keratinocytic hyperproliferation
process, which is the basis of the follicular obstruction in acne, is inhibited
by resveratrol. Inhibits hypertrophic scar formation.
Production of FFA
Lipases play an important role in pathogenesis of acne by hydrolysing sebum
triglycerides and releasing irritating free fatty acids in the pilosebaceous

2. follicles. Free fatty acids, which occupy 16% of the sebum and mainly consist
of palmitic acid, stearic acid and oleic acid.
Tetracyclines have been the most common systemic therapy for acne due to
their beneficial clinical effects, their inhibition of lipase activity of P. acnes as
well as their inhibition of P. acnes chemotaxis. Erythromycin also inhibit the
lipase activity of P. acnes
Bellamcanda inhibits lipase formation by 52%
Oxidation of Squalene
Air and reactive oxygen species (ROS) are believed to cause sebum
oxidation. Oxidative stress can thus be considered one of the events that
triggers acne. The level of lipidic peroxidation is indicative of oxidative stress.
Studies have shown that this level increases when inflammatory conditions
are present.
When acne occurs, the production of a specific lipid, squalene, spikes. If
oxidative stress is present, this squalene is peroxidated. The molecule is
present in larger quantities on the surface of acne-prone skin and around
comedos, and even more in the case of juvenile acne. Peroxidated squalene
is highly comedogenic, with a more pronounced effect than other peroxides.
In liquid form, squalene possesses unsaturation. When oxidized, it loses that
unsaturation and its fluidity, and as a result it solidifies the sebum and
contributes to comedo formation. In addition, a correlation has been identified
between the degree of squalene peroxidation and the size of comedos.
More specifically, it has been shown that certain proanthocyanidins (OPCs)
inhibit lipidic peroxidation and modulate the activity of enzymes.
p.Acnes
Magnolia species contain two major phenolic constituents, honkiol and
magnolol, which possess strong antibacterial activity against P. acnes and P.
granulosum. Magnolol and honokiol can kill P. acnes rapidly within 10
minutes. These compounds also showed significant anti-inflammatory activity
by inhibiting P. acnes-induced secretion of proinflammatory cytokines, and
inhibit IL-8 and TNF-α.
They also inhibit the formation of proinflammatory nitric oxide. Magnolol and
honokiol show potent inhibition of the induction of inducible nitric oxide
syntheses (iNOS) and activation of NF-κB. Inhibition of NF-κB is a potent way
of reducing the production of proinflammatory mediators
Both magnolol and honokiol are strong antioxidants which inhibit the oxidation
of lipids such as squalene.
There are 3 main curcuminoids in turmeric, of which curcumin
(diferuloylmethane) is the best studied. Curcumin suppresses NF-kB
activation; it inhibits arachidonic acid metabolism via lipoxygenase and

3. scavenging of free radicals generated in this pathway; it inhibits the
production of inflammatory cytokines, TNF-a , IL-1, IL-2, IL-6, IL-8, IL-12.
Nigella sativa seed oil contains high amounts of Thymoquinone (TQ). TQ has
been shown to have potent anti-inflammatory effects through the suppression
of proinflammatory mediators such as prostaglandins. TQ has been
demonstrated to inhibit the production of essential proinflammatory mediators,
such as TNFα, giving it great potential for arresting inflammation, a well-
known phenomenon in oily and mixed skin. TQ also has potent qualities in
scavenging superoxide anions, which makes TQ a strong antioxidant.
Chaulmoogra oil is the optimal source for hydnocarpic acid, gorlic acid, and
chaulmoogric acid. These are cyclopentenyl fatty acids with unique structural
features. In combination with 5’-methoxyhydnocarpin (5’-MHC) they show a
strong antimicrobial effect against mycobacteria.
It is well recognized that P. acnes is a species that adapts well to hostile
environments. P. acnes becomes resistant to the antimicrobial agents, which
are used to fight it. The most common resistance mechanisms employed by
bacteria include enzymatic degradation or alteration of the antimicrobial,
mutation in the antimicrobial target site, decreased cell wall permeability to
antimicrobials, and active efflux of the antimicrobial across the cell membrane.
5’-MHC plays an important role in inhibiting P. acnes resistance to
antimicrobials. 5’-MHC is a multidrug resistance (MDR) inhibitor. MDR
inhibitors, of which 5’-MHC has been shown to be one of the more potent
ones, bind directly to the membrane-bound efflux pumps, thus preventing the
transport of the antimicrobial out of the cell.
Apart from showing antimicrobial effects, the cyclopentenyl fatty acids have
also been shown to have potent anti-inflammatory effects. They inhibit the
formation of TNFα and PGE2.
Manuka oil contains high amounts of flavesone, leptospermone and
isoleptospermone. These β-triketones potently kill gram-positive bacteria, an
important source of topical infections. β-triketones have shown a more potent
effect against P. acnes than the wellknown tea tree oil.
References:
Treatment of acne with special emphasis on herbal remedies
Expert Rev. Dermatol. 3(1), 111–122 (2008)
Microbiology’s principle of biofilms as a major factor in the
pathogenesis of acne vulgaris
International Journal of Dermatology 2003,42, 925–927

4. Advancement in Benzoyl Peroxide-Based Acne Treatment: Methods to
increase both efficacy and tolerability.
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Different approaches of alternative medicines in acne vulgaris treatment
Orient Pharm Exp Med (2011) 11:1–9
Glycolic acid chemical peeling improves inflammatory acne eruptions
through its inhibitory and bactericidal effects on Propionibacterium
acnes
Journal of Dermatology 2012; 39: 350–354
Lipase inhibitors for the treatment of acne
Journal of Molecular Catalysis B: Enzymatic 22 (2003) 377–384
Activities of Ten Essential Oils towards Propionibacterium acnes
and PC-3, A-549 and MCF-7 Cancer Cells
Molecules 2010, 15, 3200-3210
Acne's emerging 'fifth' factor
Burkhart, Craig G
Dermatology Times; Sep 2005; 26, 9
Turmeric and Frankincense in Inflammation: An Update
Natural Medicine Journal 2011.
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putative identification of icariin, resveratrol and salidroside as active
compounds.
Phytomedicine 19 (2012) 409– 412
Anti-inflammatory effects of ginger and rosemary extracts obtained by
supercritical fluid technology
Departamento de Processos Biotecnológicos - Faculdade de Engenharia
Química - Universidade Estadual de Campinas – Campinas – SP - 13083-
970 – Brasil
Resveratrol Mediated Reduction of collagen by inhibiting proliferation
and producing apoptosis in human hypertrophic scar fibroblasts.
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