Beneficial Effect of Lard in Androgenic Alopecia

[CreakyJoints]

Sorry I cant help you with that.

Oh, no worries at all! Thank you for all your thoughtful replies so far.

 

[Lejeboca]

Consumption of fish oil high-fat diet induces murine hair loss via epidermal fatty acid binding protein in skin macrophages

Fascinating study! Thanks much for the find.

I think it is well-constructed in terms of precisely isolating the mechanism of how and why n-3's affect hair loss. The authors were very careful in eliminating unrelated pathways suspected to affect hear loss, such as gut bacteria for which they have conducted experiments with and without antibiotic treatment and found no difference.

A few additional results worth noting from the paper:

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⋄ Female mice were experimented with first. Those fed the fish oil HFD exhibited patches of non-scarring, complete loss of hair shafts accounting for over 20% of the skin area. Then, similar was observed with male mice ... although at a reduced rate compared with female mice.​

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Figure 1:Female mice​	Figure S1:Male mice​

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⋄ PA [16:0 palmitic acid] was predominantly accumulated in epididymal fat, whereas DPA [docosapentaenoic acid] was mainly enriched in subcutaneous fat (Figure 4A), suggesting a specific skin distribution pattern of n-3 FAs.​

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Figure 4A​

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⋄ Compared with mice treated with vehicle PBS [phosphate-buffered saline[ control, mice treated with anti-TNF-a antibody successfully recovered from fish oil HFD-induced hair loss (Figures 3K and 3L).​

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Figures 3K and 3L​

 

[Mauritio]

mice treated with anti-TNF-a antibody successfully recovered from fish oil HFD-induced hair loss

interesting!

 

[md_a]

Fascinating study! Thanks much for the find.

I think it is well-constructed in terms of precisely isolating the mechanism of how and why n-3's affect hair loss. The authors were very careful in eliminating unrelated pathways suspected to affect hear loss, such as gut bacteria for which they have conducted experiments with and without antibiotic treatment and found no difference.

A few additional results worth noting from the paper:

​

⋄ Female mice were experimented with first. Those fed the fish oil HFD exhibited patches of non-scarring, complete loss of hair shafts accounting for over 20% of the skin area. Then, similar was observed with male mice ... although at a reduced rate compared with female mice.​

​

View attachment 60711​	View attachment 60708​
Figure 1:Female mice​	Figure S1:Male mice​

​

​

⋄ PA [16:0 palmitic acid] was predominantly accumulated in epididymal fat, whereas DPA [docosapentaenoic acid] was mainly enriched in subcutaneous fat (Figure 4A), suggesting a specific skin distribution pattern of n-3 FAs.​

​

View attachment 60709​

Figure 4A​

​

​

⋄ Compared with mice treated with vehicle PBS [phosphate-buffered saline[ control, mice treated with anti-TNF-a antibody successfully recovered from fish oil HFD-induced hair loss (Figures 3K and 3L).​

​

View attachment 60710​

Figures 3K and 3L​

Thanks!

5-Dodecanolide, a Compound Isolated from Pig Lard, Presents Powerful Anti-Inflammatory Properties​

Abstract​

Background: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. Methods: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). Results: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. Conclusions: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.

Discussion​

PL, a food obtained after prolonged cooking of the white adipose tissue, has been traditionally used to treat blows and inflammatory processes. The anti-inflammatory effects of PL have also been evidenced by its ability to attenuate the inflammatory response of acute lung injury in endotoxemic rats [20]. We have evidenced that PL administered topically significantly decreased the inflammation induced by zymosan injection in rats. In addition, we also observed a reduction in the diameter of inflammation focus and a greater recovery after the usage of PL as an ointment. The anti-inflammatory actions of PL are parallel to changes in oxidative stress and inflammation markers in circulating neutrophils and in the inflamed tissue. We evidenced a reduction in nitrite levels in the inflamed tissue as a consequence of the treatment with PL. Nitrite levels are an indicator of nitric oxide production, an important inflammatory mediator; high concentrations of nitrite are often related to vasodilation and inflammation [22]. No effects of PL on antioxidant enzymes or in oxidative damage markers in the inflamed zone were evidenced as a consequence of the PL treatment. However, the CAT and MPO activities in circulating neutrophils are influenced by zymosan treatment and also by PL. CAT and MPO activities have previously been used as markers of inflammation [23]. We evidenced an increase in CAT and MPO activities in circulating neutrophils after zymosan treatment. However, the treatment with PL caused a significant reduction in both enzyme activities. Previous studies have reported an increase CAT activity in neutrophils stimulated with PMA [23]. Similarly, the activity of MPO, a pro-inflammatory enzyme secreted by neutrophil degranulation that produces hypochlorous acid with antimicrobial activity [24], was also increased in circulating neutrophils as a result of zymosan-induced inflammation. It is evidenced that an excessive MPO activity is related to an increase in oxidative damage and inflammation [23,24]. PL treatment reduced neutrophil MPO activity in rats treated with zymosan. In accordance, we can state that treatment with PL reduces the inflammation induced by zymosan in the hind paws of rats by modulating the synthesis of nitric oxide in the inflamed area and the antioxidant and inflammatory capacities of circulating neutrophils.

The components of PL responsible for these anti-inflammatory effects and also the mechanisms of action involved are still unknown; however, a molecular basis for the negative regulation of inflammation by lipid peroxidation products has been proposed [25]. It is described that some products from enzymatic and non-enzymatic oxidation of fatty acids, as well as oxidized phospholipid species, could regulate the inflammatory response [12,25]. It has been evidenced that the products of the oxidative modification of phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) present a powerful anti-inflammatory effect [25]. Oxidative products of arachidonic acid inhibit TNF-α production in cells stimulated with LPS [13]. A synthetic oxidized phospholipid derivative alleviates endotoxin-induced lung injury and inhibits the development of pro-inflammatory T helper 1 cells (Th) [25]. These potential anti-inflammatory compounds of PL could be extracted using a mixture of methanol to water in adequate proportions, to ensure the extraction of free oxidized fatty acids and related derivatives. The hydroalcoholic extract from PL could contain oxidative products of fatty acids with potential anti-inflammatory properties.

The anti-inflammatory properties of the hydroalcoholic extract obtained from PL were tested in human PBMCs from healthy patients. LPS is often used as inflammatory response inductor, inasmuch as to induce the production of several cytokines, such as both Th1 (such as IFNγ, TNFα, and IL8) and Th2-type cytokines (such as IL4) [26,27]. In this sense, we have evidenced an important increase in IL6, IL8, and in TNFα production in PBMCs stimulated with LPS. However, the hydroalcoholic extract obtained from PL significantly ameliorated this production of pro-inflammatory cytokines. These results suggest that some compounds present in the hydroalcoholic extract exert strong anti-inflammatory effects. In fact, it has been evidenced that products from the oxidation of lipids have anti-inflammatory effects [12,13]. In addition, we also evidenced that the hydroalcoholic extract induces an increase in PGE1 production. PGEs are lipid mediators synthesized through the oxidation of AA [28]. PGE1 has powerful vasodilatory effects, with the ability to reduce platelet and immune cell aggregation, as well as to reduce edema formation and exert anti-inflammatory effects [5,29,30,31].

We analyzed the composition of the hydroalcoholic extract obtained from PL in order to determine which compounds could be the responsible for its anti-inflammatory effects. In this sense, we detected several compounds from the fatty acids oxidation, such as 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, 6-octadecenoic acid, 9,12-octadecadienoic acid, octadecanoic acid, 5,8,11,14-eicosatetraenoic acid, 7-hexadecenoic acid, 11 acid, 14-octadecadienoic, and hexadecanamide, which were not present in white adipose tissue. Moreover, other compounds, such as resolvin D1, increase their concentration during the manufacturing process of PL present in the white adipose tissue. Several compounds detected in the PL hydroalcoholic extract have anti-inflammatory properties. Oleamide suppresses the lipopolysaccharide-induced expression of iNOS and COX-2 through the inhibition of NFkβ activation in BV2 murine microglial cells [32,33]. The 9-octadecenoic reduces the pro-inflammatory gene expression in LPS-stimulated PBMCs [34]. Compounds from the oxidation of eicosapentaenoic and docosahexaenoic acids, such as resolvin D1, maresins, and protectins, are able to reduce the production of pro-inflammatory cytokines [5,34,35,36]. The anti-inflammatory properties of PL extract could be related with the presence of resolvin D1, oleamide, and 9-octadecenoic, but we also investigated the possible anti-inflammatory effect of other PL components, such as 5-dodecanolide.

The anti-inflammatory properties of isolated resolvin D1, 5-dodecanolide, and oleamide were assayed in neutrophils stimulated with LPS using concentrations equivalent to those found in hydroalcoholic extract. Neutrophils play an important role in the development of inflammation, in immune regulation, and in tissue reparation [1,35]. The phagocytic neutrophil function involves an oxidative burst carried out by the enzyme NADPH-oxidase and the secretion of lysosomal enzymes, such as proteases, phospholipases, and glycosidases, among others [34]. Neutrophils are the first cells mobilized against tissue damage or infection, causing an inflammatory response, which is characterized by the release of the content of their granules to the external environment and in an oxidative burst consisting of the production of large amounts of hydrogen peroxide and hypochlorite with high oxygen consumption [37,38]. LPS stimulation increased CAT and MPO activities in the culture medium. The addition of the hydroalcoholic extract, oleamide, and 5-dodecanolide significantly reduced the CAT activity in the extracellular medium, although it should be noted that the greatest decrease was observed after treatment with the complete hydroalcoholic extract. MPO activity in the extracellular medium significantly decreased with the addition of the three pure compounds tested, all of them presenting effects of similar magnitude to those observed with the hydroalcoholic extract.

5-dodecanolide is evidenced as a new anti-inflammatory molecule present in the PL extract. The effects of different concentrations of 5-dodecanolide on the TNF-α production capacity of neutrophils stimulated with LPS were analyzed. The treatment with LPS significantly increased the production of TNF-α by neutrophils; this increase was attenuated by the presence of 5-dodecanolide in the culture medium. The inhibitory effects of 5-dodecanolide on TNF-α production are dose-dependent, with greater inhibition being observed at higher concentrations of 5-dodecanolide. The 5-dodecanolide, also known as 5-dodecalactone or dodecan-5-olide, belongs to the class of delta valerolactones; thus, 5-dodecanolide is considered to be a fatty ester lipid molecule, which could be a new anti-inflammatory for topical use. Outside of the human body, 5-dodecanolide has been detected, but not quantified in, several different foods, such as alcoholic beverages, fruits, herbs and spices, milk and milk products, and now in PL. The use of 5-dodecanolide to attenuate skin aging could be considered because of its relevant associated anti-inflammatory actions. A hazard evaluation of 5-dodecanolide performed by laboratory studies with rats, rabbits, and guinea pigs showed mild skin but not ocular irritation, absence of photochemical irritation in rabbits, and no sensitization reactions in guinea pigs, and did not demonstrate acute toxicity after ingestion [39].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658921/

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WO2017121916A1 - Pharmaceutical composition comprising 5-dodecanolide, preparation thereof and use of same - Google Patents

The invention relates to a pharmaceutical composition comprising 5-dodecanolide as an active ingredient. This active ingredient is isolated from pig lard using a specific treatment. The invention, therefore, also relates to a method for obtaining the composition of the invention, and to the use...

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