Do We Know Enough About Rhubarb?

NOPE! That's why the topic of rhubarb is good for us to use a a working example as study the technology of intelligence gathering and knowledge engineering.

We do know a few things about rhubarb, but what we know is not remotely enough and it's mostly because we have been looking at rhubarb as do we other pharmaceuticals ... WRONGLY ... the whole approach that we see in pharmaceuticals is WRONG because it's based on the search for the magic pill, ie the simple thing that people can swallow and the problems disappear ... and this approach is inherently WRONG because it's not an approach based on understanding LIFE ... the pharmaceutical approach is based on making a killing selling magic pills to idiots who want to swallow crap and believe experts so that their problems will magically go away ... there's no trust in LIFE, no trust in our Creator, no diligence in terms of getting to root cause and understanding how things work. The pharmaceutical approach is DEADLY ... and idiotically lazy ... and devoid of faith ... and easy ... because lazy fucks demand easy, rather than understanding how things work.

So what we know about rhubarb is that if someone is stupid enough to take massive amounts of rhubarb extracts OR stupid enough to eat rhubarb leaves ... then there are problems, especially with the oxalates ... but consuming something in a stupid fashion does not mean that it doesn't have benefits ... it's means that the pharmaceutical approach to just swallowing magic potions is something that will and should make people miserable.

When you believe in things that you don't understand, you will SUFFER.

So what does the pharmaceutical industry think they know about rhubarb?

Table of Contents

Introduction

Rhubarb (also named Rhei or Dahuang) is one of the most ancient and important herbs in traditional Chinese medicine (TCM). It belongs to the Rheum L. genus from the Polygonaceae family, and its application can be traced back to 270 BC in "Shen Nong Ben Cao Jing". Rhubarb has long been used as an antibacterial, anti-inflammatory, anti-fibrotic and anticancer medicine in China. However, for a variety of reasons, such as origin, variety and processing methods, there are differences in the effective components of rhubarb, which eventually lead to decreased quality and poor efficacy.

Global Geographic Distribution of Rhubarb

According to the Global Biodiversity Information Facility database, 23 rhubarb species are recorded. Rhubarb species including R. tanguticum Maxim., R. officinale Baill., R. palmatum L., R. acuminatum Hook. f. & Thomson, and R. australe D. Don are mainly distributed in Europe and the southwestern area of China, while R. rhabarbarum L. and R. rhaponticum L. are distributed widely across Europe to North America and part of Asia, showing obviously different geographical distributions.

As the distribution center of rhubarb, there are 39 species and 2 varieties in China, most of which are concentrated in northwest and southwest China. Three species of Rheum, including R. tanguticum Maxim., R. officinale Baill., and R. palmatum L., have been officially adopted into both the Chinese Pharmacopoeia and Korean Pharmacopoeia using the common drug name "Dahuang".

Taxonomic Identification

Traditional and Classic Methods

The quality of traditional Chinese medicine (TCM) is closely related to its variety and origin. Traditional methods used to identify rhubarb are mainly based on the characteristics of the flowers, leaves, cross-sections of roots, and crystal characteristics of the powder. The characteristics of the leaves and flowers can be used to identify different species of rhubarb, which was recorded in "Zhi Wu Ming Shi Tu Kao", a Chinese botanical work initially published in 1848.

The 10th China Pharmacopoeia Committee introduced three methods to identify rhubarb: 1) the first two methods are based on their root cross-sectional characteristics and powder crystal morphology; 2) the third method is thin-layer chromatography (TLC), which requires five major orange fluorescent spots on the chromatographic phase at the same location as the control, and exposure to ammonia vapor turns the orange to red.

Modern Identification Methods

The information provided by the traditional qualitative methods is too limited to distinguish plant species with similar appearances or chemical compositions. Various methods have been proposed for the quantitative determination of the five major anthraquinones based on high-performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEC), TLC, and many other methods.

HPLC remains the mainstream analytical method for rhubarb. HPLC coupled with many detectors, such as ultraviolet (UV), diode array detector (DAD), capillary electrophoresis (CE), and mass spectrum (MS), has been developed, which makes it more possible to detect the different components. The fingerprint method for the systematic study of the chemical constituents of TCMs can be used to indicate the chemical characteristics of TCMs by chromatogram or spectrogram.

Pharmacology

Regulation of Bacterial Action

Rhubarb has efficient antibacterial activities against a variety of bacteria, including Staphylococcus aureus, bifidobacteria, Lactobacillus, Helicobacter pylori, Escherichia coli, methicillin-resistant Staphylococcus aureus and multidrug-resistant Helicobacter pylori. Rhubarb can inhibit the growth of Staphylococcus aureus by destroying its bacterial cell wall structure and changing the permeability of the cell membrane.

In addition, the effect of rhubarb on the human gut microbiota is complex and diverse. The homeostasis of gut microbiota is conducive to inhibiting the growth of pathogenic bacteria in the intestinal tract and maintaining host energy, metabolic homeostasis, and the immune system.

Regulating Gastrointestinal Function

The main medicinal effect of rhubarb on the gastrointestinal tract is to promote the digestion of residual food. Anthraquinone compounds in rhubarb, including sennosides, rheinosides and anthraquinone aglyconesa, have efficient laxative effects by promoting intestinal contraction and movement. Furthermore, anthraquinone compounds can stimulate the submucosal nerve plexus, reduce the conductance of K+ channels on the cell membrane and enhance the electrical excitability of intestinal smooth muscle cells.

The intestinal mucosal barrier is composed of the epithelial barrier, immune barrier, intestinal flora barrier and chemical barrier, which have the function of separating the contents in the intestinal cavity and preventing the invasion of pathogenic antigens. Many clinical and animal experiments have proven that rhubarb could protect the intestinal mucosal barrier.

Anti-inflammatory Activity

In recent years, the underlying mechanisms of the anti-inflammatory effects of rhubarb have attracted more attention. Kolodziejczyk-Czepas et al. reviewed the anti-inflammatory effects of rhaponticin and the aglycone rhapontigenin and concluded that their anti-inflammatory effects were induced by inhibiting cyclooxygenase (COX), lipoxygenase (LOX) and hyaluronoglucosaminidase (HYAL) activation and modulating a variety of pro-inflammatory responses.

Various other components of rhubarb have anti-inflammatory effects, such as emodin, rhein, chrysophanol, and aloe emodin. These components work through multiple pathways to reduce inflammation, including the PPAR-γ/NF-κB/HDAC3 axis, inhibition of IκBα degradation, and regulation of MAPK phosphorylation.

Anti-fibrotic Activity

Fibrosis is the common outcome of chronic liver injury, chronic kidney disease, pulmonary interstitial disease and other chronic diseases. Rhubarb alleviates fibrosis by inhibiting or reversing the necrosis of parenchymal cells, reducing the activation and migration of monocytes to damaged tissues, inhibiting the activation of fibroblasts, relieving collagen deposition, and promoting the degradation of collagen.

Emodin, a key component of rhubarb, alleviates pulmonary fibrosis by increasing the expression of Smad7 and thereby silencing the TGF-β/Smad pathway. It also inhibits the activation of myofibroblasts by downregulating the phosphorylation of STAT3 and further decreases the synthesis of collagen by reducing the expression of HSP-47.

Antitumor Activity

Rhubarb has a strong inhibitory effect on a variety of tumors in the digestive, respiratory and reproductive systems, such as human stomach cancer, pancreatic cancer, nasopharyngeal carcinoma, lung adenocarcinoma, and ovarian carcinoma. Rhubarb plays vital roles in multiple biological processes of tumor development through several pathways and targets.

It inhibits the growth of tumor cells, suppresses tumor invasion and migration, and even hinders the formation of tumor neovascularization. These antitumor responses may be attributed to a variety of antitumor chemicals extracted from rhubarb, such as emodin, rhein, aloe emodin, and distyrene.

Clinical Applications

Constipation

Rhubarb contains a large number of anthraquinone chemical constituents, which have a strong purgatory function. Rhubarb powder and peppermint oil are commonly used to treat constipation caused by thoracolumbar fracture, type 2 diabetes or acute stroke. A meta-analysis of 850 constipation patients based on 10 randomized controlled trials (RCTs) showed that the regimen was effective in treating constipation, and no serious adverse events were reported in any trial.

Severe Acute Pancreatitis

Severe acute pancreatitis (SAP) is a common clinical acute abdominal disease with a mortality rate as high as 20%-30%. A large number of clinical studies have shown that rhubarb enema can reduce serum inflammatory cytokines, high sensory C-reactive protein (CRP) and endotoxin levels, and relieve the systemic inflammatory stress response and restore intestinal mucosal barrier function in SAP patients.

Clinically, the combination of rhubarb and the basic treatment for SAP is commonly used to increase the therapeutic effect. Two meta-analyses involving nearly 2000 SAP patients were conducted to evaluate the efficacy and safety of trypsin inhibitors or somatostatin combined with rhubarb in the treatment of SAP, and the results showed that this treatment can significantly reduce hospital stay, mortality and serum amylase levels in SAP patients.

Sepsis

Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, and the gastrointestinal tract is an important target organ for promoting SIRS after infection. A meta-analysis sorting out the treatment information of 869 patients in 15 RCTs showed that rhubarb was effective in the adjuvant treatment of sepsis. Prothrombin time and proinflammatory factor (such as IL-6 and TNF-α) levels significantly decreased and platelet count markedly increased after rhubarb administration.

Another randomized double-blind experiment randomly selected 40 eligible sepsis patients and found that rhubarb can reduce intestinal mucosal permeability in patients with sepsis, thereby reducing bacterial toxin translocation and alleviating symptoms in patients with sepsis.

Chronic Renal Failure

The common pathology of chronic renal failure (CRF) is renal fibrosis, which involves the glomerulus and renal interstitium. Rhubarb has unique advantages in improving the early symptoms of CRF and delaying the progression of renal failure. The potential mechanisms include inhibition of renal fibrosis, promotion of toxin excretion, recovery of metabolic disorders, protection of renal cells from excessive inflammation and oxidative stress damage.

Rhubarb is mainly administered by retention enema in the treatment of CRF, and the dose should depend on the number of defecation times of the patient per day. Shenkang injection, a kind of TCM that is extracted and refined from rhubarb, astragalus, Salvia miltiorrhiza and safflower, has shown promising results in clinical studies.

Others

Oral rhubarb rhizome extract significantly reduced glycosylated hemoglobin, fasting glucose, and body weight in patients with type 2 diabetes. Rhubarb liquid nasal infusion combined with montmorillonite powder and blood purification can rapidly remove the toxins in patients with organophosphorus pesticide poisoning, reduce adverse reactions and shorten the length of stay in the hospital. Clinical studies have also shown benefits in treating respiratory distress syndrome, cholestatic hepatitis, hepatic encephalopathy, and other conditions.

Safety Issues

Preclinical studies have shown that rhubarb has toxic effects on the liver and kidneys and is associated with cancer risk. Emodin, the main causative agent of rhubarb hepatotoxicity, can cause apoptosis in normal human L02 cells and increase the expression of liver injury markers. It can affect the oxidative phosphorylation pathway by inhibiting the activity of all mitochondrial complexes, which causes mitochondrial damage.

Oral rhubarb or rhubarb products pose a risk of nephrotoxicity due to the abundance of oxalates and anthraquinones, which can lead to deterioration of kidney function as a result of oxalate excretion disorder and crystal deposition in the kidney. However, renal dysfunction due to the above causes has been reported only in children or patients with mild renal disease who have been taking large amounts of rhubarb for a long time.

Whether rhubarb has a cancer risk has been controversial for nearly 30 years. A large number of preclinical studies have shown that rhubarb anthraquinones have mutagenic and genotoxic effects, and long-term administration of anthraquinone laxatives may damage epithelial cells and induce gastric cancer and colorectal cancer. However, few studies evaluating the possible carcinogenic effects of anthranoid laxatives have been performed in humans.

Conclusion and Perspective

Rhubarb is widely distributed across Europe, North America and part of Asia, and the species from different origins are obviously different. Much effort has been focused on the identification of these various species in recent years. Among them, chemical fingerprint and metabonomic identification methods can reflect the origin and hybrids of rhubarb, respectively.

Rhubarb has been used to interfere with the development of various diseases, including SAP, sepsis, and CRF, due to its antibacterial, anti-inflammatory, and antifibrotic activities and the regulation of gastrointestinal function. However, several critical issues need to be considered in future studies.

Rhubarb has significant hepatotoxicity, which may be related to the accumulation of emodin in the liver or its influence on the oxidative phosphorylation pathway, and gender may also be a factor affecting its hepatotoxicity. Understanding the mechanisms underlying rhubarb hepatotoxicity is of great value for the clinical promotion of rhubarb.

It remains controversial whether long-term use of rhubarb can cause cancer. In addition, the existing literature on the clinical application of rhubarb is mostly based on the experience of doctors and lacks uniform standards. More scientific, rigorous and extensive clinical trials are needed to gain better insights into the therapeutic potential and safety of rhubarb.