Physalis angulata L.: From Traditional Remedy to Modern Medicine's New Frontier
In the tangled undergrowth of tropical fields, a humble weed holds secrets that scientists are just beginning to unravel.
Imagine a plant so versatile that it can treat diabetes, fight cancer cells, and calm inflammation—all while producing a delicious fruit encased in a papery lantern. This is Physalis angulata L., a widespread medicinal plant that grows wild across tropical and subtropical regions worldwide.
Global Names
- Indonesia: Ciplukan
- Brazil: Camapú
- United States: Cutleaf groundcherry
- Other names: Winter cherry, wild tomato
Traditional Uses
- Diabetes management
- Hypertension treatment
- Anti-inflammatory applications
- Respiratory conditions
Known by many names, this unassuming member of the nightshade family has captured the attention of both traditional healers and modern scientists 1 . For generations, indigenous communities have harnessed its healing properties, while contemporary research is now validating these traditional uses through rigorous scientific investigation.
The Plant with a Bladder: Getting to Know Physalis angulata
The name "Physalis" derives from the Greek word for 'bladder,' perfectly describing the inflated, lantern-like calyx that encloses its fruit 1 . This annual herb grows up to one meter tall with angular stems, oval-lanceolate leaves, and small bell-shaped flowers that develop into edible berries wrapped in the characteristic papery cover 3 .
While it might resemble a common weed, Physalis angulata has been deeply integrated into traditional medicine systems across the cultures that know it. In Indonesia, it's used to treat diabetes, hypertension, and various inflammatory conditions 5 . In Peruvian Amazon communities, it manages diabetes, nervous system disorders, and asthma 3 . Traditional Chinese medicine employs it for its antipyretic, anti-inflammatory, and diuretic properties 1 .
Nature's Chemical Factory: Bioactive Components of Physalis angulata
The therapeutic potential of Physalis angulata stems from its rich profile of bioactive compounds, particularly secondary metabolites that the plant produces as defense mechanisms. Through advanced analytical techniques like UHPLC-ESI-QTOF-MS, researchers have identified dozens of compounds distributed throughout the plant's roots, stems, leaves, and fruits 3 .
Physalins
These are 13,14-seco-steroids—steroids with a broken ring structure—that are considered the most important and distinctive compounds in Physalis species . Multiple physalins (A through I, and others) have been isolated from Physalis angulata, with physalins B, D, and F being particularly studied for their potent biological activities 1 .
Withanolides
These are C-28 ergostane-type steroids with a δ-lactone group at C-22 and C-26 6 . Like physalins, withanolides demonstrate impressive bioactive properties and have become targets for drug development.
Key Bioactive Compounds and Their Effects
| Compound Class | Specific Examples | Primary Biological Activities |
|---|---|---|
| Physalins | Physalin B, D, F | Antibacterial, anticancer, anti-inflammatory, immunomodulatory |
| Withanolides | Withangulatin A, Physagulin A-G | Anticancer, anti-inflammatory, enzyme inhibition |
| Flavonoids | Myricetin 3-O-neohesperidoside | Antioxidant, enzyme inhibition |
| Phenolic Compounds | Various phenolic acids | Antioxidant, free radical scavenging |
A Pharmacological Powerhouse: Proven Bioactivities of Physalis angulata
Modern laboratory studies have substantiated many of the traditional uses of Physalis angulata, revealing a remarkable range of pharmacological activities through both in vitro (test tube) and in vivo (animal) studies.
Antimicrobial Warrior
Physalis angulata demonstrates significant antibacterial properties against various pathogens. Research shows that extracts, particularly from leaves and calyces, inhibit growth of bacteria including Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli 1 .
Cancer Fighter
Perhaps the most promising area of research involves the anticancer potential of Physalis angulata compounds. Multiple studies have demonstrated that extracts and isolated compounds can inhibit the growth of various cancer cell lines through inducing apoptosis, disrupting cell cycle progression, and activating caspase pathways 1 .
Inflammation Regulator
The anti-inflammatory properties of Physalis angulata are well-documented. A 2025 study demonstrated that fruit extract could alleviate sepsis-associated acute lung injury in mice by modulating macrophage polarization and inhibiting key inflammatory pathways 9 .
Documented Pharmacological Activities
| Activity | Plant Part Used | Experimental Model | Key Findings |
|---|---|---|---|
| Anticancer | Leaves | HeLa cells (cervical cancer) | LC50 of 44 µg/ml; induced apoptosis 1 |
| Antibacterial | Whole plant | Staphylococcus aureus | Zone of inhibition: 17.00±0.0 mm with 70% ethanol extract 1 |
| Anti-inflammatory | Fruits | LPS-induced mouse model of lung injury | Reduced inflammatory markers; modulated macrophage polarization 9 |
| Antioxidant | Leaves | DPPH assay | 85% radical scavenging activity for ethanolic extract 6 |
| Antidiabetic | Whole plant | Alloxan-induced diabetic rats | Improved renal function; antioxidative effects 4 |
Comparative Bioactivity of Plant Parts
Inside the Lab: A Closer Look at a Key Anti-Inflammation Study
To understand how researchers uncover the therapeutic potential of plants like Physalis angulata, let's examine a recent groundbreaking study published in Phytomedicine in 2025 that investigated the fruit's anti-inflammatory potential 9 .
Extract Preparation
Fruits of Physalis angulata were dried, powdered, and extracted with 80% ethanol aqueous solution using reflux extraction. The resulting extract (designated EPAF) was concentrated and analyzed using HPLC-Q-TOF-MS/MS to identify major chemical constituents.
In Vivo Testing
Researchers established a mouse model of sepsis-associated acute lung injury (ALI) using lipopolysaccharide (LPS) induction. Mice were treated with EPAF at different doses (25, 50, or 100 mg/kg) to evaluate the extract's protective effects.
Cellular Mechanisms
To understand how EPAF works, investigators examined its effects on macrophage polarization—the process where immune cells switch between pro-inflammatory (M1) and anti-inflammatory (M2) states. They specifically focused on PFKFB3, a key glycolytic enzyme that drives inflammation.
Pathway Analysis
The team analyzed how EPAF affects critical signaling pathways (NF-κB, HIF-1α, and STAT3) known to regulate inflammation and immune responses.
Key Findings
- EPAF significantly attenuated LPS-induced lung injury in mice, reducing tissue damage and inflammatory cell infiltration.
- The extract shifted macrophage polarization from the pro-inflammatory M1 state toward the anti-inflammatory M2 state.
- EPAF modulated the acetylation and phosphorylation of PFKFB3, which in turn affected glycolysis and subsequent activation of inflammatory pathways.
Research Significance
This research is significant because it not only demonstrates the efficacy of Physalis angulata fruit in treating severe inflammation but also elucidates the molecular mechanism behind this effect. The findings position EPAF as a promising candidate for developing treatments for inflammatory conditions like sepsis and acute lung injury.
Essential Research Reagents and Methods
| Reagent/Method | Primary Function | Application Example |
|---|---|---|
| UHPLC-ESI-QTOF-MS | High-resolution chemical profiling | Identifying physalins and withanolides in plant extracts 3 |
| Solvent Extraction Systems | Extracting different compound classes | Using petroleum ether, ethyl acetate, and ethanol for sequential extraction 6 |
| Cell Culture Models | Testing bioactivity in controlled systems | Evaluating anticancer effects on HeLa, MCF-7, DLD-1 cancer lines 1 6 |
| Animal Disease Models | Studying complex physiological effects | LPS-induced lung injury models for inflammation studies 9 |
From Lab Bench to Marketplace: Intellectual Property and Commercial Applications
The demonstrated bioactivities of Physalis angulata have generated significant commercial interest, evidenced by a growing number of patent applications covering various extracts, isolated compounds, and their applications.
Patent Landscape
Patent databases reveal 28 patents related to Physalis angulata, with the highest concentration in the A61K category (cosmetics and pharmaceuticals) 4 .
Commercial Focus
This patent activity indicates a clear pathway from traditional use to commercial development, with particular emphasis on dermatological, anti-inflammatory, and anticancer applications.
Patent Applications Include:
Extraction Methods
For physalins and other active compounds 7Anti-inflammatory Compositions
For treating skin conditions like atopic dermatitis 8Isolated Compounds
Like "Physalin angulata L. I" with anti-inflammatory activity 2Cosmetic Applications
Targeting sensitive skin and allergic reactions 8Conclusion: A Promising Future for an Ancient Remedy
Physalis angulata L. represents a perfect example of how traditional knowledge and modern science can converge to identify promising therapeutic agents. From its humble beginnings as a folk remedy, it has evolved into a subject of intense scientific investigation, with research validating its antibacterial, anticancer, anti-inflammatory, and metabolic-regulating properties.
The future research landscape for Physalis angulata appears vibrant. Scientists are working to:
- Standardize extraction protocols for consistent bioactive profiles
- Elucidate precise molecular mechanisms of its active compounds
- Develop clinical formulations for specific therapeutic applications
- Address conservation challenges through sustainable cultivation practices
As research continues to unravel the complexities of this botanical treasure, Physalis angulata stands as a testament to nature's pharmacy—reminding us that sometimes the most promising medicines don't come from high-tech laboratories, but from the ancient wisdom of plants that have healed for generations.