Hair Loss; Exploring TCM approaches

First post, thanks Lucas for posting insights on TTFD—among MANY other useful nutrients, which—otherwise I simply would never have heard of—let alone learned about.

Part 1/4

Within the context of the title, beyond the life-logged black box of ‘before—after’ pics, this may help identify relevant biomarkers for hair loss, without looking too broadly upstream, e.g., type XVII collagen (COL17), or by increment downstream, e.g., SMAD proteins (Smad2/3), the latter likely more precise with scope for greater selectivity. Lateral co-factors, e.g., Hic-5/ARA55. So while by no means exhaustive, acknowledging the many potential pathways, inter alia—the more practical mechanisms—so as to effectively ‘target’ (molecules), these include;

  1. DKK-1 (Dickkopf-related protein 1)
  2. TGF-ß1, TGF-ß2 via Hic-5/ARA55/ARA70
  3. Wnt/ß-catenin, Wnt5a (primary), Wnt1a/3a/4/7b/10a–b (secondary)
  4. 5ar-type2 (5-alpha reductase type-2) or SRD5∂2

†source; doi: 10.1111/ics.12489, doi: 10.3390/ijms21144915, doi: 10.1016/j.jdermsci.2011.08.010

N.B. Hic-5/ARA55 "Hic-5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp.” —there may be something in this ‘site-specificity’, the article concludes “…Hic-5/ARA55 is a molecular regulator for androgen sensitivity in human hair follicles.” Which I see was previously (briefly) explored on Longecity. Additionally, “Hic‐5 promotes fibrosis by activating the TGF‐β/Smad, while inhibiting Smad7”.

†source; doi: 10.1038/sj.jid.5700883, doi: 10.3892/ijmm.2022.5194

—Fibrosis? it’s without question connected to dihydrotestosterone, but, I wonder what the evolutionary adaptation, or vestigial exaptation’s (behind this) are—the environmental stressors, for males having increased sensitivity of AR Hic-5/ARA55/ARA70 in the presence of DHT in the occipital region. Perhaps more importantly, then, what of other tissues and organs where ARA55/ARA70 is also expressed. You’re still going to need some kind of strategy to either mitigate, ameliorate—or to prevent from happening that otherwise would.

HDAC inhibitors have been usefully discussed on Peat. Which explains why caffeine, niacinamide are used in some topical applications. While the OP on Longecity—making the connec using HDCA inhibitors—suppressing occipital androgen receptor (AR) co-activator Hic-5, as important as that may be, however giving short shrift to other candidates. Although to be fair, the OP didn’t distinguish between highly localised site-specific external application—and internal systems-wide and global in effect. I think it has legs…

†doi 10.1007/s12263-012-0283-9 (table 2)
note; doesn’t explicitly mention HDACi’s which activate Hic-5/ARA55 * ARA70
or get into the pharmacokinetics, molecular weight, half-life, niacin is short right?

Note to self; drink coffee, yerba—hibiscus, supp. niacin

To bifurcate an otherwise complex process; DKK-1 and TGF-ß2 relates to apoptotic cell death—hair loss can be caused by their activation, whereas VEGF, IGF-1, and Wnt5∂ (activation) are associated with promoting the hair growth cycle. E.g., the “ectopic expression of Dickkopf 1 (DKK1), which inhibits Wnt action [36,37,38,39,40] by binding with LRP co-receptor”. Provisional research implicates LRP 5/6 receptors. DHT, therefore, causing ER-related stress?

Conversely, the deactivation (inhibition) of TGF-ß2, the TGF-ß2 antagonists allow hair to proliferate. Within the dermal papilla; TGF-ß2 via DHT, triggering pro-apoptotic caspases.
The article referencing three aspects (levels) of the “catagen cascade" for possible intervention. The third (level) appears universal, involving ‘cell-death’ caspases, and ‘cell survival’, and repair—hypothetically speaking—working backwards, allosteric modulation of Bcl-2, p53, etc… —to AR antagonists, the competitive inhibitors of DHT binding to androgenic receptors ‘outcompeting’ DHT (binding affinity).

†doi: 10.1016/j.jdermsci.2003.12.003

Reading between the lines of ‘systemic’ and ‘localised’ delivery, theoretically, the micro-environment plays a part—requiring adequate circulation, the angle of approach is four-fold, E.g., 1) systemic enzyme strategies ought be beneficial, —to dampen thrombin, or break up fibrin, ‘fibrinolytics’. 2) Anti-calcification; Internally, hydroxycitrate or EDTA, chlorella—i.e., the Cutler (‘Andrew Hall Cutler’) protocol. Externally—calcium chelator’s like aerosolised ACV or DMSO, and 3) reduce blood-platelet viscosity, PDE-5 inhibitors, etc… In sum, these may potentially lay the preparatory groundwork for superior efficacy of macro-nutrient perfusion, or penetration. 4) Anaerobic exercise (HIIT), radio calisthenics, vurtego V4 like super mario, and if pushed—a triple-axis aerotrim.

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Part 2/4

Over here, in the UK, we’ve a hair tonic (brand) called Herbal hair® essentially re-packaging the Beijing-based ‘ZhangGuang 101®’ for European markets. It’s subtle—understated, one that’s easy to overlook. I’ve not (yet) taken an Alice-like swan dive into the science, i.e., cross-referencing, collating, tabulating ‘listed’ nutrients (dermatology, trichology journal insights), anecdotally on baidu, bilibili… connecting the dots to relevant molecules, (then) transcribing those (transcription factors) to relevant molecular pathways and cascades—attributing causal relations, if any… AI LLMs/OpenAI’s ChatGPT 4.0, Baidu’s Wenxinyiyan (Ernie Bot) ought to get a handle on this— ‘duck soup’. So ran a quick experiment, a conversation piece with ChatGPT primarily focused on this brand of hair tonic very much in the TCM tradition.

https://yiyan.baidu.com —smartphone required for access
https://fanyi.baidu.com/mtpe-individual/multimodal —Baidu’s English—Chinese translator

A complete molecular teardown of the functional aspects of ALL bioactive components (101® series) would likely take some time. That said, I kinda got the impression from reading their (english) blog—, ‘Red Sage’ (Dan Shen) performs much of the heavy-lifting for the growth-phase, given the pattern of whatever shrinks the prostate is likely good for your hair. By extension, and vice-versa, it’s possible the Tanshinone IIA downregulates (degrading) the androgen receptors (AR) on the scalp assuming the therapeutic target. Other molecular mechanisms, Dan Shen also possessing the capacity to reduce testosterone induced TNF-α and IFN-γ intercellular inflammation (ROS) via Nrf-2/ARE

† source; doi: 10.4014/jmb.2308.08053, doi: 10.1155/2018/7309073
† the ISAFCHM database may help here, also
‘Dietary Chinese Herbs’, Chemistry, Pharmacology and Clinical Evidence
Yanze Liu, Zhimin Wang & Junzeng Zhang (2015)
*there’s an evaluation copy floating around on the internet

Regardless; the topical ingredients for 101G are—

  1. Radix Ginseng (人参) ‘ren shen’ (panax ginseng)
  2. Radix Salviae Miltiorrhizae (丹參) ‘dan shen’ (red sage)
  3. Radix Sophorae Flavescentis (苦参) ‘ku shen’ (sophora flavescens)
  4. Flos Carthami (红花) ‘honghua’ (safflower)
  5. Radix Saposhnikoviae (防风) ‘fang feng’ (siler root)
  6. Radix Polygoni Multiflori (何首乌) ‘he shou wu’ (fo-ti)
  7. Flos Chrysanthemi (甘菊花) ‘gan ju hua’ (wild chrysanthemum)
  8. Radix Gentianae (龙胆草) ‘long dan cao’ (gentian root)

The medicinal tea ‘Ju Hua Shan Zha Cha’, comprising Chrysanthemi Flos (甘菊花) and Crataegi Fructus (山楂). The phenolic content is said to be super potent.

† doi; 10.1016/j.jtcme.2014.10.001

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Part 3/4

How Herbal Hair Works – Herbal Hair,
Perhaps this better explains the differences between the various sub-brands; 101—the original tonic (regrowth), 101B (prevention) & 101G (cleansing). https://herbalhair.com/blogs/news/which-herbs-are-best-for-hair-loss-prevention, the blog—adding more depth.

N.B. they also sell the oral supplement ‘Qi Bao Mei Ran Dan’, which appears an inferior truncation of the classic ‘Yang Xue Sheng Fa’ —the small black spherical pills. In the first instance— ‘Fo-ti’ is largely best avoided ‘internally’. Latterly, I was advised by a TCM practitioner this ‘Yang Xue Sheng Fa’ increases circulatory health, for a propitious micro-environment for hair to flourish (taken internally). Ingredients include—;

Rehmannia Gluinosa (熟地) ‘shu di huang’ (rehmannia)
Angelica Sinensis (当归) ‘dang gui’ (dong quai)
Paeonia Lactiflora (白芍) ‘bai shao’ (white peony)
Lingusticum Wallichii (川芎) ‘chuan xiong’ (szechuan lovage)
Cuscuta Chinensis (菟丝子) ’tu si zi’ (c. chinensis)
Luctus Lyci (枸杞⼦) ‘gou ji zi’ (goji berry)
Fructus Chaenomelis (木瓜) ‘mu gua’ (chaenomeles speciosa)
Paeonia Suffruticosa (牡丹皮) ‘mu dan pi’ (tree peony—root)
Dioscorea Opposita (山药) ‘shan yao’ (chinese yam)
Poria Cocos (茯苓) ‘ fu ling’ (poria)

† Always curious by the interesting properties of parasites, holoparasites—fascinating stuff. Cuscuta chinensis—to a lesser extent, the wood-decay fungus ‘poria’. Recent research drew attention to the 4-part decoction, Shenmayizhi (参麻 益智汤), demonstrating potential for mitochondrial biogenesis, isolating the molecule Ginsenoside ‘—Rd’. Although not expressly focused on hair per se—which is to say ‘in general terms’, the article concludes; “Puerarin, ligustrazine, baicalin and catalpol showed clear anti-apoptosis effect.” Analysing ‘Figure 3’ may throw up hypothetical scenarios, particularly around the role of CREBs (cyclic adenosine phosphate-response element binding protein), in relation to Cyt C (cytochrome c).

† doi; 10.3389/fphar.2023.1138566

Even for those who don’t fully subscribe to TCM principles, for whatever reason, the active attempt to understand the science, there is a clear sense of things being directionally right—if not molecularly refined. Personally I use the ‘house’ shampoo from Napiers, Edinburgh (Scotland) adding to that—their red sage. Go Scottish economy… with a bicapil™ (sculletaria) hair mask—also adding red sage, then neat ACV as conditioner every few days or so, which kinda works for me. It would lilely benefit from some ground-down, or powdered Soy bean solution (daily) in an Ethan Hawke, Gattaca–esque regimen for the VEGF.

Anyone (else) use 101® B/G? How do (did) you find it?

Here’s my following conversation with OpenAI’s ChatGPT… chatting breeze…

Part 4/4

/Me/
“Are you familiar with the Beijing-based ZhangGuang 101® Haircare products? 101, 101B, and 101G…”

/ChatGPT/
Yes, I’m familiar with ZhangGuang 101® Haircare products. These products, developed by Dr. Zhao Zhangguang, are well-known in China and internationally for their purported effectiveness in promoting hair growth and treating various hair loss conditions. Here’s an overview of some of the key products:
ZhangGuang 101® Haircare Products

  1. 101
    • Description: This is the original formula, known for its ability to promote hair growth and improve the overall health of the scalp and hair follicles.
    • Ingredients: Typically includes herbal ingredients such as ginseng, angelica, and various other Chinese medicinal herbs.
    • Uses: Primarily used to treat androgenic alopecia (male and female pattern baldness) and other types of hair loss.

  2. 101B
    • Description: A variation of the original formula, designed to be more potent and effective for more severe cases of hair loss.
    • Ingredients: Similar to the original formula but with adjusted concentrations and possibly additional ingredients to enhance effectiveness.
    • Uses: Recommended for individuals with significant hair thinning and more advanced stages of hair loss.

  3. 101G
    • Description: Another specialized formula focusing on improving hair density and strength while also promoting growth.
    • Ingredients: Also based on traditional Chinese medicine, this product may have unique additives targeting specific scalp conditions.
    • Uses: Often used by those looking to not only regrow hair but also improve the overall thickness and health of existing hair.

General Benefits and Features
• Herbal-Based: All products in the ZhangGuang 101® line emphasize the use of traditional Chinese medicinal herbs, reputed for their natural healing properties.
• Scalp Health: These products aim to improve scalp circulation, reduce dandruff, and create a healthier environment for hair growth.
• Clinical Use: Widely used in clinical settings within China for the treatment of various hair loss conditions.

Usage and Application
• Application: Typically, the products are applied directly to the scalp, with specific instructions for massage and frequency provided by the manufacturer.
• Consistency: Regular and consistent use is often recommended to see noticeable results over time.

Market and Availability
• Global Reach: While these products are very popular in China, they are also available in international markets, often through specialized importers or online platforms.
• Reputation: They have a strong following and are often recommended by practitioners of traditional Chinese medicine.

Effectiveness
• User Reviews: Effectiveness can vary from person to person. Many users report positive results, but as with any hair care product, outcomes can depend on individual conditions and adherence to the treatment regimen.

• Clinical Studies: Some clinical studies support the efficacy of these products, but it’s important to review independent studies and consult healthcare professionals for personalized advice.

In summary, ZhangGuang 101® haircare products are well-regarded, particularly in the realm of traditional Chinese medicine, for their approach to treating hair loss and promoting hair health using herbal ingredients.

/Me/
The topical ingredients for 101G are;— 1) Radix Ginseng (人参) ‘ren shen’ (panax ginseng) 2) Radix Salviae Miltiorrhizae (丹參) ‘dan shen’ (red sage) 3) Radix Sophorae Flavescentis (苦参) ‘ku shen’ (sophora flavescens) 4) Flos Carthami (红花) ‘honghua’ (safflower) 5) Radix Saposhnikoviae (防风) ‘fang feng’ (siler root) 6) Radix Polygoni Multiflori (何首乌) ‘he shou wu’ (fo-ti) 7) Flos Chrysanthemi (甘菊花) ‘gan ju hua’ (wild chrysanthemum) 8) Radix Gentianae (龙胆草) ‘long dan cao’ (gentian root)

Can you list the ingredients in similar vein for the original 101® product?

/ChatGPT/
The ZhangGuang 101® Haircare product is renowned for its use of traditional Chinese medicinal herbs. While the exact formulation can be proprietary and subject to changes, the original 101® product typically includes the following key ingredients:

Ingredients of the Original ZhangGuang 101®
1. Radix Ginseng (人参) ‘ren shen’ (Panax Ginseng)
2. Radix Angelicae Sinensis (当归) ‘dang gui’ (Angelica Sinensis)
3. Radix Salviae Miltiorrhizae (丹參) ‘dan shen’ (Red Sage)
4. Radix Polygoni Multiflori (何首乌) ‘he shou wu’ (Fo-ti)
5. Fructus Ligustri Lucidi (女贞子) ‘nu zhen zi’ (Glossy Privet Fruit)
6. Radix Rehmanniae (地黄) ‘di huang’ (Rehmannia Root)
7. Radix Astragali (黄芪) ‘huang qi’ (Astragalus Root)
8. Radix Glycyrrhizae (甘草) ‘gan cao’ (Licorice Root)
9. Radix Angelicae Pubescentis (独活) ‘du huo’ (Pubescent Angelica Root)
10. Fructus Cnidii (蛇床子) ‘she chuang zi’ (Cnidium Fruit)

Benefits of Key Ingredients
• Radix Ginseng (人参) ‘ren shen’ (Panax Ginseng): Known for stimulating hair growth, improving blood circulation, and strengthening hair follicles.
• Radix Angelicae Sinensis (当归) ‘dang gui’ (Angelica Sinensis): Promotes blood circulation and provides essential nutrients to the scalp.
• Radix Salviae Miltiorrhizae (丹參) ‘dan shen’ (Red Sage): Improves scalp health and enhances hair growth.
• Radix Polygoni Multiflori (何首乌) ‘he shou wu’ (Fo-ti): Traditionally used to prevent hair loss and promote hair pigmentation.
• Fructus Ligustri Lucidi (女贞子) ‘nu zhen zi’ (Glossy Privet Fruit): Helps to nourish the liver and kidneys, improving overall hair health.
• Radix Rehmanniae (地黄) ‘di huang’ (Rehmannia Root): Nourishes the blood and has anti-aging properties.
• Radix Astragali (黄芪) ‘huang qi’ (Astragalus Root): Strengthens the immune system and supports hair growth.
• Radix Glycyrrhizae (甘草) ‘gan cao’ (Licorice Root): Soothes the scalp and reduces inflammation.
• Radix Angelicae Pubescentis (独活) ‘du huo’ (Pubescent Angelica Root): Relieves pain and improves blood circulation.
• Fructus Cnidii (蛇床子) ‘she chuang zi’ (Cnidium Fruit): Traditionally used to treat scalp conditions and promote healthy hair growth.

These ingredients work synergistically to improve scalp health, stimulate hair follicles, and promote robust hair growth. The formulation leverages the principles of traditional Chinese medicine to address both the symptoms and underlying causes of hair loss.

/Me/
That was useful… And again in similar fashion for ZhangGuang’s 101B

Certainly! Here are the ingredients commonly found in ZhangGuang’s 101B formulation, presented in a similar manner to the original 101® product:
Ingredients of ZhangGuang 101B®
1. Radix Ginseng (人参) ‘ren shen’ (Panax Ginseng)
2. Radix Angelicae Sinensis (当归) ‘dang gui’ (Angelica Sinensis)
3. Radix Polygoni Multiflori (何首乌) ‘he shou wu’ (Fo-ti)
4. Radix Rehmanniae (地黄) ‘di huang’ (Rehmannia Root)
5. Radix Salviae Miltiorrhizae (丹參) ‘dan shen’ (Red Sage)
6. Fructus Ligustri Lucidi (女贞子) ‘nu zhen zi’ (Glossy Privet Fruit)
7. Radix Angelicae Pubescentis (独活) ‘du huo’ (Pubescent Angelica Root)
8. Flos Carthami (红花) ‘hong hua’ (Safflower)
9. Radix Sophorae Flavescentis (苦参) ‘ku shen’ (Sophora Flavescens)
10. Fructus Cnidii (蛇床子) ‘she chuang zi’ (Cnidium Fruit)
11. Radix Glycyrrhizae (甘草) ‘gan cao’ (Licorice Root)

Benefits of Key Ingredients
• Radix Ginseng (人参) ‘ren shen’ (Panax Ginseng): Stimulates hair growth, improves blood circulation, and strengthens hair follicles.
• Radix Angelicae Sinensis (当归) ‘dang gui’ (Angelica Sinensis): Promotes blood circulation and provides essential nutrients to the scalp.
• Radix Polygoni Multiflori (何首乌) ‘he shou wu’ (Fo-ti): Traditionally used to prevent hair loss and promote hair pigmentation.
• Radix Rehmanniae (地黄) ‘di huang’ (Rehmannia Root): Nourishes the blood and has anti-aging properties.
• Radix Salviae Miltiorrhizae (丹參) ‘dan shen’ (Red Sage): Improves scalp health and enhances hair growth.
• Fructus Ligustri Lucidi (女贞子) ‘nu zhen zi’ (Glossy Privet Fruit): Helps to nourish the liver and kidneys, improving overall hair health.
• Radix Angelicae Pubescentis (独活) ‘du huo’ (Pubescent Angelica Root): Relieves pain and improves blood circulation.
• Flos Carthami (红花) ‘hong hua’ (Safflower): Promotes blood circulation and stimulates hair growth.
• Radix Sophorae Flavescentis (苦参) ‘ku shen’ (Sophora Flavescens): Known for its anti-inflammatory and antimicrobial properties, improving scalp health.
• Fructus Cnidii (蛇床子) ‘she chuang zi’ (Cnidium Fruit): Traditionally used to treat scalp conditions and promote healthy hair growth.
• Radix Glycyrrhizae (甘草) ‘gan cao’ (Licorice Root): Soothes the scalp and reduces inflammation.

Additional Context
• Purpose: ZhangGuang 101B is formulated to be more potent than the original 101, targeting more severe cases of hair loss with a reinforced blend of traditional Chinese medicinal herbs.
• Application: Similar to other products in the ZhangGuang 101® line, it is applied directly to the scalp with specific instructions for optimal use.

These ingredients work together to enhance the health of the scalp, stimulate hair follicles, and promote the growth of strong, healthy hair. The formulation continues to adhere to the principles of traditional Chinese medicine, offering a natural approach to hair restoration.

/Me/
I notice Scutellaria baicalensis the herb and active compound baicalin is absent? Are there any advantages of adding baicalin to hair growth formulations, if so—what are the molecular mechanisms and likely signalling pathways?

/ChatGPT/
Scutellaria baicalensis, commonly known as Chinese skullcap, and its active compound baicalin, have been studied for various health benefits, including their potential in promoting hair growth. Adding baicalin to hair growth formulations could offer several advantages based on its pharmacological properties.
Advantages of Adding Baicalin to Hair Growth Formulations
1. Anti-Inflammatory Properties:
◦ Benefit: Baicalin has strong anti-inflammatory effects, which can help reduce scalp inflammation—a common cause of hair loss.
◦ Mechanism: Baicalin inhibits the production of pro-inflammatory cytokines and mediators, such as TNF-α, IL-1β, and IL-6, by modulating the NF-κB signaling pathway.
2. Antioxidant Activity:
◦ Benefit: Baicalin acts as an antioxidant, protecting hair follicles from oxidative stress.
◦ Mechanism: It scavenges free radicals and upregulates the expression of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT).
3. Promotion of Hair Follicle Growth:
◦ Benefit: Baicalin may directly stimulate the growth of hair follicles.
◦ Mechanism: Studies have shown that baicalin can extend the anagen phase (growth phase) of the hair cycle. It does this by promoting the proliferation of dermal papilla cells (DPCs), which play a crucial role in hair follicle development and cycling.
4. Inhibition of 5α-Reductase:
◦ Benefit: Baicalin inhibits the enzyme 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), a major factor in androgenic alopecia (male and female pattern baldness).
◦ Mechanism: By reducing DHT levels, baicalin helps in preventing hair follicle miniaturization and promotes hair growth.

Molecular Mechanisms and Signaling Pathways
1. Wnt/β-Catenin Pathway:
◦ Role: This pathway is critical for hair follicle development and regeneration.
◦ Baicalin’s Effect: Baicalin activates the Wnt/β-catenin signaling pathway, which promotes the proliferation and differentiation of hair follicle cells.
2. PI3K/Akt Pathway:
◦ Role: Involved in cell survival, growth, and proliferation.
◦ Baicalin’s Effect: Baicalin has been shown to activate the PI3K/Akt pathway, enhancing the survival and proliferation of hair follicle cells.
3. ERK/MAPK Pathway:
◦ Role: Regulates cell proliferation and differentiation.
◦ Baicalin’s Effect: Baicalin modulates the ERK/MAPK signaling pathway, promoting the proliferation of keratinocytes and dermal papilla cells.
4. Anti-Androgenic Effects:
◦ Mechanism: Baicalin inhibits the activity of 5α-reductase, reducing DHT levels and its deleterious effects on hair follicles.

Summary
Incorporating baicalin into hair growth formulations can provide multiple benefits through its anti-inflammatory, antioxidant, and hair follicle-stimulating properties. By influencing key signaling pathways such as Wnt/β-catenin, PI3K/Akt, and ERK/MAPK, baicalin can promote hair growth and potentially mitigate hair loss conditions, especially those related to androgenic alopecia.

/Me/
That was a great exposition, can you apply this to Red Sage, its likely effects on hair? So in similar vein let me rephrase the context around my (new) question. Radix Salviae Miltiorrhizae the herb—and active compounds, with particular focus on its Tanshinones. What are the molecular mechanisms, and likely signalling pathways?

/ChatGPT/
Radix Salviae Miltiorrhizae, commonly known as Red Sage or Danshen, contains several active compounds, with tanshinones being among the most significant. These compounds have been studied for their potential health benefits, including their effects on hair growth. Here’s a detailed examination of how tanshinones from Red Sage could benefit hair growth, focusing on their molecular mechanisms and signaling pathways.

Active Compounds in Red Sage
1. Tanshinones:
◦ Tanshinone I
◦ Tanshinone IIA
◦ Cryptotanshinone
2. Salvianolic Acids:
◦ Salvianolic Acid B
◦ Rosmarinic Acid

Potential Effects on Hair Growth
1. Anti-Inflammatory Properties:
◦ Benefit: Tanshinones possess potent anti-inflammatory effects, which can help reduce scalp inflammation and create a healthier environment for hair growth.
◦ Mechanism: Tanshinones inhibit pro-inflammatory cytokines and mediators, such as TNF-α, IL-1β, and IL-6, by suppressing the NF-κB signaling pathway.
2. Antioxidant Activity:
◦ Benefit: Tanshinones are strong antioxidants, protecting hair follicles from oxidative stress, which is a contributor to hair loss.
◦ Mechanism: They scavenge free radicals and enhance the activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT).
3. Promotion of Hair Follicle Growth:
◦ Benefit: Tanshinones may promote hair follicle growth and extend the anagen phase of the hair cycle.
◦ Mechanism: Tanshinones stimulate the proliferation and differentiation of dermal papilla cells (DPCs), which are crucial for hair follicle development and cycling.
4. Microcirculation Improvement:
◦ Benefit: Improved microcirculation enhances nutrient delivery to hair follicles, supporting hair growth.
◦ Mechanism: Tanshinones improve blood flow by promoting the relaxation of vascular smooth muscles and inhibiting platelet aggregation.

Molecular Mechanisms and Signaling Pathways
1. Wnt/β-Catenin Pathway:
◦ Role: Critical for hair follicle development and regeneration.
◦ Tanshinones’ Effect: Tanshinones may activate the Wnt/β-catenin signaling pathway, promoting the proliferation and differentiation of hair follicle cells.
2. PI3K/Akt Pathway:
◦ Role: Involved in cell survival, growth, and proliferation.
◦ Tanshinones’ Effect: Tanshinones activate the PI3K/Akt pathway, enhancing the survival and proliferation of hair follicle cells.
3. ERK/MAPK Pathway:
◦ Role: Regulates cell proliferation and differentiation.
◦ Tanshinones’ Effect: Tanshinones modulate the ERK/MAPK signaling pathway, promoting the proliferation of keratinocytes and dermal papilla cells.
4. Anti-Androgenic Effects:
◦ Mechanism: While tanshinones primarily exhibit anti-inflammatory and antioxidant effects, they may indirectly influence androgen-related pathways, reducing the negative impact of DHT on hair follicles.
5. VEGF (Vascular Endothelial Growth Factor) Upregulation:
◦ Role: VEGF promotes angiogenesis, which improves blood supply to hair follicles.
◦ Tanshinones’ Effect: Tanshinones upregulate VEGF expression, enhancing microcirculation and nutrient delivery to hair follicles.

Summary
Incorporating tanshinones from Red Sage (Radix Salviae Miltiorrhizae) into hair growth formulations can provide multiple benefits due to their anti-inflammatory, antioxidant, and hair follicle-stimulating properties. By activating key signaling pathways such as Wnt/β-catenin, PI3K/Akt, and ERK/MAPK, tanshinones can promote hair growth and potentially mitigate hair loss. Additionally, their ability to improve microcirculation and upregulate VEGF further supports their role in enhancing hair health and growth.

/Me/
This may help identify relevant biomarkers for hair loss, without looking too broadly upstream, e.g., type XVII collagen (COL17), or by increment downstream, e.g., SMAD proteins (Smad2/3), the latter likely more precise with greater selectivity. Lateral co-factors, e.g., Hic-5/ARA55. So while by no means exhaustive, acknowledging the many potential pathways, inter alia—the more practical mechanisms—so as to effectively ‘target’ (molecules), these include; 1) DKK-1 (Dickkopf-related protein 1) 2) TGF-ß1, TGF-ß2 via Hic-5/ARA55/ARA70 3) Wnt/ß-catenin, Wnt5a (primary), Wnt1a/3a/4/7b/10a–b (secondary) 4) 5ar-type2 (5-alpha reductase type-2) or SRD5∂2

I’ve four questions relating to this; Which of the ZhangGuang products would be considered most efficacious in negotiating the four or so molecular targets in view of the most propitious outcome? Are there any other mechanisms, which may yeild a viable molecular target for any of the ingredients mentioned thus far?

In this context would HDCA inhibitors be useful in any capacity? Finally, Hic-5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp.” —there may be something in this ‘site-specificity’. What is the role of Hic-5, and its relationship with TGF-ß1, and TGF-ß2?

/ChatGPT/
Addressing your questions involves delving into the specific mechanisms of hair growth regulation and the potential role of ZhangGuang products in targeting these pathways. Here’s an in-depth analysis:

  1. Which of the ZhangGuang products would be considered most efficacious in negotiating the 4 or so molecular targets in view of the most propitious outcome?
    Given the molecular targets you’ve outlined (DKK-1, TGF-ß1, TGF-ß2, Wnt/ß-catenin, and 5ar-type2), ZhangGuang 101G appears to be the most comprehensive due to its ingredients and their known effects on hair growth pathways:
    • Radix Ginseng (Panax Ginseng): Known to influence the Wnt/ß-catenin pathway and inhibit DKK-1, promoting hair growth.
    • Radix Salviae Miltiorrhizae (Red Sage): Contains tanshinones, which modulate TGF-ß signaling and potentially inhibit 5-alpha reductase activity.
    • Radix Polygoni Multiflori (Fo-ti): Traditionally believed to promote hair pigmentation and growth, potentially influencing the Wnt pathway.
    • Radix Sophorae Flavescentis (Sophora Flavescens): Exhibits anti-androgenic properties, which can inhibit 5ar-type2.

Thus, ZhangGuang 101G would likely be the most efficacious in addressing these molecular targets.
2. Are there any other mechanisms that may yield a viable molecular target for any of the ingredients mentioned thus far?
Yes, additional mechanisms and targets include:
• VEGF (Vascular Endothelial Growth Factor): Enhancing angiogenesis and improving blood supply to hair follicles. Ingredients like Red Sage can upregulate VEGF.
• Anti-inflammatory Pathways: Reducing scalp inflammation to create a better environment for hair growth. Ingredients like Licorice Root (Radix Glycyrrhizae) and Sophora Flavescens exhibit strong anti-inflammatory properties.
• Antioxidant Pathways: Protecting hair follicles from oxidative damage. Ingredients like Ginseng and Fo-ti have strong antioxidant properties.

  1. In this context would HDAC inhibitors be useful in any capacity?
    Histone deacetylase (HDAC) inhibitors could indeed be useful in promoting hair growth. HDAC inhibitors can:
    • Promote Gene Expression: By altering chromatin structure, they can enhance the expression of genes involved in hair follicle growth.
    • Modulate Wnt/ß-Catenin Pathway: HDAC inhibitors can upregulate Wnt signaling, which is crucial for hair follicle development.
    While ZhangGuang products do not explicitly contain known HDAC inhibitors, integrating such compounds could potentially enhance their efficacy.

  2. What is the role of Hic-5, and its relationship with TGF-ß1, and TGF-ß2?
    Hic-5 (Hydrogen peroxide-inducible clone 5), also known as ARA55, is a focal adhesion protein and a co-regulator of androgen receptor (AR) signaling. Its roles and relationships with TGF-ß1 and TGF-ß2 include:
    • Role in Dermal Papilla Cells:
    ◦ High in Beard and Bald Frontal Scalp: High expression correlates with androgen sensitivity, which might explain the susceptibility to androgenic alopecia in these regions.
    ◦ Low in Occipital Scalp: This region is less sensitive to androgens, correlating with lower Hic-5 expression.

    • Relationship with TGF-ß1 and TGF-ß2:
    ◦ TGF-ß Signaling Modulation: Hic-5 enhances the transcriptional activity of TGF-ß receptors. TGF-ß1 and TGF-ß2 are known to induce catagen (regression phase) in hair follicles.
    ◦ Androgen Receptor Co-Activator: Hic-5/ARA55 interacts with androgen receptors, modulating their activity and affecting hair follicle cycling.

Summary
To summarize the practical implications:
• ZhangGuang 101G is the most promising product for targeting the specified molecular pathways.
• Additional mechanisms like VEGF upregulation, anti-inflammatory, and antioxidant pathways provide further potential targets.
• HDAC inhibitors could enhance hair growth by promoting gene expression and Wnt signaling.
• Hic-5/ARA55 plays a crucial role in androgen sensitivity and TGF-ß signaling, impacting site-specific hair growth patterns and androgenic alopecia.

By focusing on these pathways and molecular targets, ZhangGuang products can be better tailored to combat hair loss and promote hair growth.

/Me/
Is ARA70 at all relevant?

/ChatGPT/
Yes, ARA70 is indeed relevant in the context of hair growth and androgen-related pathways. Here’s a detailed look at ARA70 and its significance:
Understanding ARA70
ARA70 (Androgen Receptor Coactivator 70) is a coactivator of the androgen receptor (AR), which plays a critical role in mediating the effects of androgens like testosterone and dihydrotestosterone (DHT). ARA70 enhances the transcriptional activity of the androgen receptor, impacting various biological processes, including hair growth.

Role of ARA70 in Hair Growth
1. Androgen Receptor Activation:
◦ Function: ARA70 amplifies the signaling of the androgen receptor.
◦ Impact on Hair: Androgens, particularly DHT, are known to cause hair follicle miniaturization in androgenic alopecia (pattern hair loss). By enhancing AR activity, ARA70 can potentially exacerbate hair loss in androgen-sensitive areas of the scalp.

2.TGF-ß Signaling:
◦ Interplay with Hic-5: Both ARA70 and Hic-5 are coactivators of the androgen receptor and can modulate TGF-ß signaling. TGF-ß1 and TGF-ß2 are known to induce the catagen phase of the hair cycle, leading to hair follicle regression.
◦ Implication: High ARA70 activity can enhance the effects of TGF-ß, contributing to hair follicle miniaturization and hair loss.

Molecular Mechanisms and Pathways
1. Androgen Receptor Signaling:
◦ Primary Pathway: ARA70 enhances AR-mediated transcription, affecting the expression of genes involved in hair follicle cycling and maintenance.
◦ DHT Sensitivity: Elevated ARA70 levels can increase sensitivity to DHT, leading to more pronounced hair follicle miniaturization in androgenic alopecia.
2. Interaction with Coactivators and Corepressors:
◦ Complex Formation: ARA70 interacts with other coactivators like Hic-5 and corepressors, forming complexes that regulate gene expression.
◦ Modulation of Hair Growth: These interactions can modulate various signaling pathways, including Wnt/ß-catenin and TGF-ß, impacting hair growth and cycling.

Implications for Hair Loss Treatment
1. Targeting Androgen Receptor Pathway:
◦ Potential Inhibition: Inhibitors of AR or modulators that decrease ARA70 activity could potentially reduce hair loss by mitigating androgen receptor activation.
◦ Combination Therapy: Combining such inhibitors with other treatments that target different pathways (e.g., Wnt/ß-catenin activation) could provide a comprehensive approach to treating hair loss.
2. Balancing Coactivator Activity:
◦ Therapeutic Strategies: Modulating the balance of coactivator activity (e.g., ARA70, Hic-5) may help in managing hair growth. Reducing the activity of coactivators that enhance AR signaling while promoting pathways that favor hair growth (e.g., Wnt signaling) could be beneficial.

Summary
ARA70 is highly relevant in the context of hair growth and androgen-related pathways. It enhances androgen receptor activity, impacting hair follicle cycling and contributing to androgenic alopecia. By understanding the role of ARA70 and its interaction with other coactivators like Hic-5, we can better target treatments for hair loss. Potential therapeutic approaches include inhibiting AR signaling, modulating coactivator balance, and combining treatments that address multiple pathways affecting hair growth.

/Me/
Consider what we’ve discussed so far. How are the popular compounds coffee—caffeine and niacin—niacinamide still relevant? Would they add anything new, over and above all existing ingredients; compounds and chemicals?

/ChatGPT/
Caffeine and niacinamide are popular compounds commonly found in hair care products, and they do offer unique benefits that can complement the effects of the other ingredients discussed. Here’s an analysis of their relevance and potential advantages when integrated with the existing compounds and chemicals:

Caffeine
Mechanisms of Action:
1. DHT Inhibition:
◦ Mechanism: Caffeine can inhibit the enzyme 5-alpha reductase, which converts testosterone to DHT. By reducing DHT levels, caffeine helps prevent hair follicle miniaturization and hair loss associated with androgenic alopecia.
◦ Complementarity: This mechanism aligns well with the anti-androgenic properties of other ingredients like Radix Salviae Miltiorrhizae and Radix Sophorae Flavescentis.
2. Stimulation of Hair Follicles:
◦ Mechanism: Caffeine stimulates hair follicle keratinocyte proliferation by promoting cell growth and extending the anagen (growth) phase of the hair cycle.
◦ Signaling Pathways: Caffeine may influence the Wnt/ß-catenin signaling pathway, further promoting hair growth.
3. Microcirculation Improvement:
◦ Mechanism: Topical caffeine application improves blood circulation to the scalp, enhancing nutrient delivery to hair follicles.
◦ Synergy: This complements the microcirculation benefits provided by ingredients like Flos Carthami (safflower) and Radix Salviae Miltiorrhizae (Red Sage).

Niacinamide (Vitamin B3)
Mechanisms of Action:
1. Improvement of Scalp Health:
◦ Mechanism: Niacinamide enhances the health of the scalp by improving the skin barrier function, increasing ceramide and free fatty acid levels, and reducing transepidermal water loss.
◦ Complementarity: A healthy scalp provides a better environment for hair growth and complements the anti-inflammatory properties of other ingredients like Radix Glycyrrhizae (licorice root).
2. Anti-Inflammatory Properties:
◦ Mechanism: Niacinamide has anti-inflammatory effects, which help reduce scalp inflammation and irritation.
◦ Signaling Pathways: It may inhibit inflammatory cytokines and modulate NF-κB signaling, enhancing the anti-inflammatory effects of ingredients like Radix Salviae Miltiorrhizae and Radix Sophorae Flavescentis.
3. Stimulation of Hair Follicle Growth:
◦ Mechanism: Niacinamide can improve blood flow to the scalp and enhance follicular nutrition, promoting hair growth.
◦ Synergy: This effect is similar to the benefits provided by caffeine and complements the microcirculation enhancement provided by other ingredients.

Integration with Existing Ingredients
1. Enhanced Anti-Androgenic Effects:
◦ Caffeine: Works alongside Radix Salviae Miltiorrhizae and Radix Sophorae Flavescentis in reducing DHT levels, providing a multi-faceted approach to androgenic alopecia.
2. Improved Scalp Health and Inflammation Reduction:
◦ Niacinamide: Augments the anti-inflammatory properties of Radix Glycyrrhizae and other ingredients, creating a healthier scalp environment conducive to hair growth.
3. Synergistic Hair Follicle Stimulation:
◦ Caffeine and Niacinamide: Both compounds promote hair follicle health and growth, complementing the effects of ingredients like Radix Ginseng and Radix Polygoni Multiflori, which influence the Wnt/ß-catenin pathway.
4. Enhanced Microcirculation:
◦ Caffeine and Niacinamide: Both improve blood flow to the scalp, enhancing the nutrient and oxygen supply to hair follicles, which works synergistically with Flos Carthami and Radix Salviae Miltiorrhizae.

Conclusion
Caffeine and niacinamide add significant value to hair growth formulations through their unique mechanisms of action. Caffeine’s ability to inhibit DHT and stimulate hair follicles complements the anti-androgenic and growth-promoting effects of other traditional Chinese medicine ingredients. Niacinamide’s benefits for scalp health, anti-inflammatory properties, and blood flow enhancement further support the overall efficacy of the formulation. Integrating these compounds can provide a more comprehensive and effective approach to promoting hair growth and preventing hair loss.

Fin.

†the original Chinese url; www.zg101.com, the archive can be found at https://web.archive.org/web/www.101hair.com

1 Like

Awesome break down and definitely a lot of actionable steps here. Have you tried this with any success yet?